Retinal Function Research Articles

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration

BackgroundThe retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration.MethodsLD was induced by exposing mice to 4000 lx of light for 2–4 hours (h). IBU (100 or 200 mg/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). Cell death genes were analyzed at 24 and 72 h after LD using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of key necroptosis genes were assessed by immunohistochemistry.ResultsRetinal outer nuclear layer (ONL) thickness in vehicle-injected LD animals was 8.7 ± 0.6% of retinas without LD (p < 0.0001). In IBU 200 mg/kg treated mice, central ONL thickness was 74.9 ± 7.7% of untreated retinas (p < 0.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hour after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1B), and C-C motif chemokine ligand 2 (Ccl2) increased by 10-, 17-, and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including Ripk3 and Mlkl, were upregulated in LD vehicle-treated mice, but dramatically reduced to near no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12 h after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas.ConclusionsSystemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.

Advancing Insights into Pediatric Macular Diseases: A Comprehensive Review.

Pediatric macular disorders are a diverse group of inherited retinal diseases characterized by central vision loss due to dysfunction and degeneration of the macula, the region of the retina responsible for high-acuity vision. Common disorders in this category include Stargardt disease, Best vitelliform macular dystrophy, and X-linked retinoschisis. These conditions often manifest during childhood or adolescence, with symptoms such as progressive central vision loss, photophobia, and difficulty with fine visual tasks. Underlying mechanisms involve genetic mutations that disrupt photoreceptor and retinal pigment epithelium function, accumulating toxic byproducts, impaired ion channel activity, or structural degeneration. Advances in imaging modalities like optical coherence tomography and fundus autofluorescence have improved diagnostic accuracy and disease monitoring. Emerging therapies are transforming the treatment landscape. Gene therapy and genome editing hold promise for addressing the genetic basis of these disorders, while stem cell-based approaches and pharmacological interventions aim to restore retinal function and mitigate damage. Personalized medicine, driven by genomic sequencing, offers the potential for tailored interventions. Despite current challenges, ongoing research into molecular mechanisms, advanced imaging, and innovative therapies provides hope for improving outcomes and quality of life in children with macular disorders.

Longitudinal assessment of retinal and visual pathway electrophysiology and structure after high altitude exposure.

High altitude (HA) exposure induces impairments in visual function. This study was designed to dynamically observe visual function after returning to lowland and elucidate the underlying mechanism by examining the structure and function of retina and visual pathway. Twenty-three subjects were recruited before (Test 1), and one week (Test 2) and three months (Test 3) after their return from HA (4300m) where they resided for 30 days. The clock task was used to assess visual cognition; and pattern-reversal visual evoked potential (p-VEP) and full-field electroretinogram (ff-ERG) were employed to record electrophysiological responses of retinal cells; optical coherence tomography (OCT), color doppler imaging (CDI) and magnetic resonance imaging(MRI) were used to measure structures of retina and visual pathway. In Test 2 vs. Test 1, there was increased reaction time during angle task; the amplitudes of scotopic 3.0cd·s/m2 and scotopic 10.0cd·s/m2 ERG a-wave and scotopic 3.0cd·s/m2 oscillatory potential in the right eye were significantly decreased, all of which were negatively correlated with the increased reaction time during the angle task. In Test 3 vs. Test 1, there were decreased amplitude of scotopic 10.0cd·s/m2 a-wave in the right eye and increased velocity of ophthalmic artery and ocular perfusion pressure in bilateral eyes. The VEP and visual pathway structures remained normal throughout the entire test. HA exposure caused damage to rod and cone responses in both outer and inner retina. After returning to sea level, the damaged visual cell functions gradually recovered over time, coinciding with an increase in the ocular perfusion.

Optimized PLGA encapsulated SA-2 nanosuspension exhibits sustained intraocular pressure reduction in the mouse microbead occlusion model of ocular hypertension.

Elevated intraocular pressure (IOP) is implicated in the structural and functional damage to the retinal ganglion cells (RGCs) in primary open-angle glaucoma (POAG). Topical IOP lowering agents provide short-term relief, necessitating frequent dosing. Moreover, non-adherence to frequent eyedrops administration contributes significantly to visual field loss and worsens the disease outcome. We optimized the poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulation of hybrid antioxidant-nitric oxide donor SA-2 (SA-2NP), investigated its bioavailability, duration of IOP lowering efficacy, and effects on retinal function in the microbead model of ocular hypertension (OHT). SA-2 was bioavailable in the anterior and posterior segments after 1, 8, and 24 h post-single topical eyedrop administration. SA-2NP significantly lowered IOP (∼25-34%) and preserved the RGC function after weekly eyedrop administration for 3 weeks in C57BL/6J mice. In conclusion, the optimized SA-2NP formulation demonstrated optimal bioavailability, ocular safety, and prolonged IOP-lowering efficacy in the mouse microbead occlusion model of OHT.

A Hydrogel-Based Multiplex Coculture Platform for Retinal Component Cells.

There is growing interest in generating in vitro models of tissues and tissue-related diseases to mimic normal tissue organization and pathogenesis for different purposes. The retina is a highly complex multicellular tissue where the organization of the cellular components relative to each other is critical for retinal function. Many retinopathies arise due to the disruption of this order. In this study, we aimed to generate a coculture model of retina-derived cells, namely RPE and Müller cells, in multiplexed 3D hydrogels. Using methacrylated gelatin (GelMA)-based 3D hydrogels, we compared the behavior of RPE and Müller cells when they were cultured together. These patterned multiplex hydrogels containing cells were cultured for several days to reflect how cells would reorganize themselves in the presence of another cellular component derived from the same tissue. Here, we present a multicellular multiplex platform for the creation of cellular networks with cells of retinal tissue that can be easily adapted to create more complex tissue-like alternatives for large-scale tissue modeling and screening purposes. We also present an alternative method of coculture by generating spheroids from one of the components while keeping the other component free and motile in the hydrogel. The latter model predicts enhanced possibilities of cellular interactions by retarding the movement of one of the component cells.

A Case of Concomitant Acute Zonal Occult Outer Retinopathy and Secondary Nonparaneoplastic Autoimmune Retinopathy

Introduction: Acute Zonal Occult Outer Retinopathy (AZOOR) is a rare inflammatory retinal disease with rapid outer retinal function loss, photopsias, unremarkable fundus findings, and electroretinography (ERG) abnormalities. AZOOR diagnosis can be challenging due to its overlap with other retinal conditions, such as acute idiopathic blind spot enlargement syndrome (AIBES) and autoimmune retinopathies (AIRs). Multimodal imaging, including fundus autofluorescence (FAF) and optical coherence tomography (OCT), has improved detection, revealing progressive outer retinal damage. Although the etiology of AZOOR remains uncertain, autoimmune mechanisms and viral associations have been proposed. Recent studies have identified anti-retinal antibodies, complicating differentiation from other autoimmune retinopathies.. Case Presentation: A 63-year-old male presented with photopsias, floaters, and worsening vision in his left eye. He had a prior diagnosis of autoimmune retinopathy with serum antibodies against enolase, arrestin, and heat shock protein 27 (HSP27). Despite corticosteroid therapy, his visual acuity worsened from 20/20 to 20/60. Fundus examination showed subtle changes, and multimodal imaging revealed outer retinal damage consistent with AZOOR. He was started on mycophenolate mofetil, cyclosporine, and intravenous immunoglobulin (IVIg). Over a year of follow-up, his vision improved to 20/25, and imaging showed stabilization of retinal damage. Conclusion: This case report highlights AZOOR can be associated with secondary npAIR. Multimodal imaging, electrophysiologic testing of retina and RPE, and anti-retinal antibody may be helpful for diagnosis of these patients. A combination of conventional immunomodulatory therapy and IVIg can help with controlling AZOOR and secondary npAIR.

Novel Anti-Microbial/Anti-Inflammatory Combination Improves Clinical Outcome of Bacillus cereus Endophthalmitis.

The purpose of this study was to explore the therapeutic potential of the novel combination of Bacillus bacteriophage lysin (PlyB) and a synthetic TLR2/4 inhibitor (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, OxPAPC) in the treatment of experimental Bacillus cereus endophthalmitis. C57BL/6J mice were injected with 100 colony forming units (CFUs) Bacillus cereus to induce endophthalmitis. Two hours postinfection, groups of mice were treated with either PlyB, PlyB with OxPAPC, or the groups were left untreated to serve as a control. A group of uninfected mice was injected with only PlyB to serve as a treatment control. Eight hours post-treatment, infected/treated mice were analyzed for bacterial counts, retinal function, histology, and inflammation. Groups treated with PlyB alone or PlyB/OxPAPC showed significantly reduced bacterial loads compared with untreated eyes. Compared with untreated eyes, PlyB and PlyB/OxPAPC-treated eyes retained significant A-wave and B-wave function. PlyB/OxPAPC-treated eyes retained greater A- and B-wave function compared with eyes treated with PlyB alone. Histology showed that retinal structures were well preserved, and retinal layers were distinguishable in eyes treated with PlyB and PlyB/OxPAPC. Ninety-five percent of infiltrating CD45+ cells in infected untreated eyes were Ly6G+/Ly6C+ neutrophils. Infected eyes treated with PlyB and PlyB/OxPAPC had significantly reduced numbers of CD45+ immune cells compared with untreated eyes. Eyes treated with PlyB/OxPAPC had a significantly lower number of neutrophils than eyes treated with PlyB alone. These results demonstrated that the novel combination of bacteriophage lysin and TLR2/4 inhibitor was a successful treatment option for treating experimental Bacillus cereus endophthalmitis.

Genetic Characteristics of 63 Patients with Non-syndromic Retinitis Pigmentosa at a Single Korean Institution

Purpose: To investigate the genetic characteristics of patients with non-syndromic retinitis pigmentosa (RP) analyzed at a single institution.Methods: We conducted a retrospective analysis of 63 patients clinically diagnosed with non-syndromic RP who underwent genetic testing. The clinical features of patients exhibiting the most common mutations, &lt;i&gt;EYS&lt;/i&gt; and &lt;i&gt;USH2A&lt;/i&gt;, were further assessed through routine ophthalmic examinations.Results: Of the 63 patients, 22 (34.9%) exhibited significant mutations. Notably, &lt;i&gt;EYS&lt;/i&gt; and &lt;i&gt;USH2A&lt;/i&gt; mutations were each found in 5 patients (7.9%); &lt;i&gt;RP1&lt;/i&gt; mutations were found in 4 patients (6.3%). The average ages at diagnosis were 38.8 years for &lt;i&gt;EYS&lt;/i&gt; mutations and 41.8 years for &lt;i&gt;USH2A&lt;/i&gt; mutations. The average best-corrected visual acuities were logMAR 0.08 for &lt;i&gt;EYS&lt;/i&gt; mutations and logMAR 0.51 for &lt;i&gt;USH2A&lt;/i&gt; mutations. Both mutation types showed a decrease in the normal macular area in fundus photographs with increasing age. In &lt;i&gt;USH2A&lt;/i&gt; mutations, optical coherence tomography revealed a more pronounced reduction in central macular thickness and central foveal ellipsoid length compared with &lt;i&gt;EYS&lt;/i&gt; mutations. Visual field tests indicated a reduction within the central 10° in 40% of &lt;i&gt;EYS&lt;/i&gt; mutations and 60% of &lt;i&gt;USH2A&lt;/i&gt; mutations. Electroretinography showed non-detectable responses in 2 individuals with &lt;i&gt;EYS&lt;/i&gt; mutations and 4 individuals with &lt;i&gt;USH2A&lt;/i&gt; mutations (40% and 80%, respectively).Conclusions: &lt;i&gt;EYS&lt;/i&gt; and &lt;i&gt;USH2A&lt;/i&gt; mutations represented 45% of the genetically identified cases; affected patients typically were diagnosed in their 40s. &lt;i&gt;EYS&lt;/i&gt; mutations tended to preserve retinal function and central foveal structure better than &lt;i&gt;USH2A&lt;/i&gt; mutations.

Broadband Long Wavelength Light Promotes Myopic Eye Growth and Alters Retinal Responses to Light Offset in Chick.

Prolonged exposure to broadband light with a short-wavelength (blue) or long-wavelength (orange/red) bias is known to impact eye growth and refraction, but the mechanisms underlying this response are unknown. Thus, the present study investigated the effects of broadband blue and orange lights with well-differentiated spectrums on refractive development and global flash electroretinography (gfERG) measures of retinal function in the chick myopia model. Chicks were raised for 4 days with monocular negative lenses, or no lens, under blue, orange, or white light. Chick weight, eye dimensions, and refraction were measured at the conclusion of rearing. In a separate cohort of chicks, the effect of 4 days of colored light rearing on retinal responses to orange, blue, or white light flashes was assessed using gfERG. Chicks reared under orange light for 4 days exhibited a significantly larger myopic shift in response to negative lenses compared to those reared under blue light. Orange light rearing for 4 days increased the gfERG d-wave amplitude and implicit time in response to orange light flashes but did not alter responses to white or blue flashes. Blue and white light rearing did not affect the retina's response to light flashes of any color. Orange light rearing exacerbated defocus-induced myopia relative to blue light rearing. The gfERG recordings revealed that prolonged orange light exposure increased retinal responsivity to the offset of long wavelength light flashes, suggesting a potential role for ON/OFF pathway balance in generating the refractive response that requires further electrophysiological and molecular investigation.

Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model.

Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.

Managing Retinitis Pigmentosa: A Literature Review of Current Non-Surgical Approaches.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by the progressive loss of photoreceptor function, visual impairment, and, ultimately, blindness. While gene therapy has emerged as a promising therapy, it is currently available only for the RPE65 gene mutation, leaving many patients without targeted genetic treatments. Non-surgical interventions may help in managing the progression of RP and improving patients' quality of life. Visual training and rehabilitation, maximizing residual vision, have shown potential in improving mobility and patients' ability to perform daily activities. Visual aids enhance visual function. Moreover, photo-protection demonstrated effectiveness in mitigating light-induced damage and improving visual comfort. Alternative therapies (i.e., electrostimulation, acupuncture, and ozone therapy) are being explored to preserve retinal function and reduce disease progression. Pharmacological interventions supported by nutritional and psychological counseling play a role in slowing retinal degeneration while managing the emotional burden of progressive vision loss. Although for these interventions, further validation is required, their potential benefits make them valuable additions to care for RP patients. The integration of these interventions into a multidisciplinary care approach-including ophthalmologists, orthoptist, dietitians, and psychologists-is essential for providing comprehensive, personalized care to RP patients while awaiting more widespread gene therapy solutions.

Retinal OCT-Derived Texture Features as Potential Biomarkers for Early Diagnosis and Progression of Diabetic Retinopathy.

Diabetic retinopathy (DR) is usually diagnosed many years after diabetes onset. Indeed, an early diagnosis of DR remains a notable challenge, and, thus, developing novel approaches for earlier disease detection is of utmost importance. We aim to explore the potential of texture analysis of optical coherence tomography (OCT) retinal images in detecting retinal changes in streptozotocin (STZ)-induced diabetic animals at "silent" disease stages when early retinal molecular and cellular changes that cannot be clinically detectable are already occurring. Volume OCT scans and electroretinograms were acquired before and 1, 2, and 4 weeks after diabetes induction. Automated OCT image segmentation was performed, followed by retinal thickness and texture analysis. Blood-retinal barrier breakdown, glial reactivity, and neuroinflammation were also assessed. Type 1 diabetes induced significant early changes in several texture metrics. At week 4 of diabetes, autocorrelation, correlation, homogeneity, information measure of correlation II (IMCII), inverse difference moment normalized (IDN), inverse difference normalized (INN), and sum average texture metrics decreased in all retinal layers. Similar effects were observed for correlation, homogeneity, IMCII, IDN, and INN at week 2. Moreover, the values of those seven-texture metrics described above decreased throughout the disease progression. In diabetic animals, subtle retinal thinning and impaired retinal function were detected, as well as an increase in the number of Iba1-positive cells (microglia/macrophages) and a subtle decrease in the tight junction protein immunoreactivity, which did not induce any physiologically relevant effect on the blood-retinal barrier. The effects of diabetes on the retina can be spotted through retinal texture analysis in the early stages of the disease. Changes in retinal texture are concomitant with biological retinal changes, thus unlocking the potential of texture analysis for the early diagnosis of DR. However, this requires to be proven in clinical studies.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose. Twelve WT pigs (24 eyes) were divided into three groups: four pigs each received bilateral subretinal injections of either vehicle, low dose (3.3 × 1010 vector genomes [vg] per eye), or high dose (1.0 × 1011 vg per eye). Total retinal thickness (TRT) was evaluated using optical coherence tomography and retinal function was assessed with full-field electroretinography (ff-ERG) at baseline and two months post-surgery. After necropsy, retinal changes were examined through histopathology, and human USH1C_a1/harmonin expression was assessed by quantitative PCR (qPCR) and Western blotting. OT_USH_101 led to high USH1C_a1 expression in WT pig retinas without significant TRT changes two months after subretinal injection. The qPCR revealed expression of the human USH1C_a1 transgene delivered by the adeno-associated virus vector. TRT changes were minimal across groups: vehicle (256 ± 21 to 243 ± 18 µm; P = 0.108), low dose (251 ± 32 to 258 ± 30 µm; P = 0.076), and high dose (242 ± 24 to 259 ± 28 µm; P = 0.590). The ff-ERG showed no significant changes in rod or cone responses. Histopathology indicated no severe retinal adverse effects in the vehicle and low dose groups. Early-phase clinical imaging, electrophysiology, and histopathological assessments indicated that subretinal administration of OT_USH_101 was well tolerated in the low-dose treatment arm. OT_USH_101 treatment resulted in high expression of human USH1C_a1. Although histopathological changes were not severe, more frequent changes were observed in the high-dose group.

Hydroxytyrosol-Rich Olive Mill Wastewater, a Potential Protector Against Dyslipidemia, Diabetes, and Diabetic Retinopathy in Psammomys obesus.

Olive mill wastewater (OMWW), a byproduct of olive oil extraction, constitutes a natural resource of phenolic compounds. Hydroxytyrosol (HT), the predominant compound, was reported to have antioxidant, anti-inflammatory, and neuroprotective effects. This research aims to evaluate the effect of OMWW bioproduct rich in HT on retinal glial function, glutamate metabolism, and synaptic transmission alterations mediated by hyperglycemia and dyslipidemia in high-calorie diet (HCD)-induced diabetic retinopathy (DR) in Psammomys obesus. Animals were divided into four groups. Two diabetic animal groups (D) received an HCD, one untreated (D) and another receiving HT-OMWW treatment (20mg/kg body weight: bw) (D+); the two other groups were used as controls (C and C+). During 7 months, food and water intake, body weight, glycemia, hematocrit, and serum lipid parameters were assessed. At 3, 5, and advanced 7 months of DR, immunohistochemical studies were performed to identify key proteins implicated in the protection of DR. HT-OMWW has anti-obesity, hypoglycemic, and hypolipidemic effects. Its long-term administration attenuates retinal glial reactivity, microglia number, changes in glutamate homeostasis, and synaptic function in diabetic animals with retinopathy. These results suggest that HT-OMWW extract seems to have promising in vivo anti-diabetic, anti-dyslipidemic, and neuroprotective effects in P. obesus, a model of DR-like humans.

CAMK2D and Complement Factor I-Involved Calcium/Calmodulin Signaling Modulates Sodium Iodate-Induced Mouse Retinal Degeneration.

To investigate the effect of Ca2+/calmodulin-dependent protein kinase II (CAMKII) δ subtypes (CAMK2D) on sodium iodate (NaIO3)-induced retinal degeneration in mice. Bioinformatics analysis and Western blot experiments were used to screen the significantly differentially expressed genes in age-related macular degeneration (AMD) disease. CAMK2D knockdown and overexpression models were constructed by lentivirus (LV) infection of adult retinal pigment epithelial cell line-19 (ARPE-19) cells in vitro. Flow cytometry was used to detect ARPE-19 cell apoptosis induced by NaIO3. In vivo, CAMK2D knockdown and overexpression mouse models were generated by infecting mouse retinal pigment epithelium (RPE) with adeno-associated virus (AAV). Retinography, optical coherence tomography (OCT), and histological analysis (hematoxylin and eosin staining) were used to detect NaIO3-induced retinal structural changes in mice. Electroretinography (ERG) was used to detect NaIO3-induced retinal function changes in mice. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of retinal cells induced by NaIO3. RNA sequencing (RNA-Seq) and bioinformatics analysis were used to screen for target genes affected by CAMK2D in CAMK2D-overexpressing ARPE-19 cells. And flow cytometry, OCT, and ERG were used to evaluate the regulatory effect of CAMK2D on target genes. Bioinformatics analysis found the expression of genes related to Ca2+ signal was significantly reduced in AMD patients. Western blot showed that in a mouse model of dry AMD induced by NaIO3, CAMK2D expression in RPE-Choroid tissue significantly lower than normal mice. In vitro, our results showed that overexpression of CAMK2D in ARPE-19 cells decreased apoptosis induced by NaIO3 and knockdown increased apoptosis. In vivo, CAMK2D overexpression in RPE cells can attenuate the retina degeneration induced by NaIO3 and CAMK2D knockdown aggravated degeneration. The bioinformatics analysis indicated that CAMK2D might affect AMD pathology through complement factor I (CFI). In vitro, knockdown of CFI in ARPE-19 cells increased apoptosis induced by NaIO3. In knockdown CFI ARPE-19 cells, overexpression of CAMK2D reduced the above apoptosis. In mice retina, CFI knockdown can aggravate the retina degeneration induced by NaIO3. In knockdown CFI mice, overexpression of CAMK2D in RPE can attenuate the above retina degeneration. Western blot confirmed that CAMK2D regulated the expression of CFI in mice. CAMK2D can attenuate the retinal degeneration induced by NaIO3, which was achieved by regulating the CFI.

The retinal structure and visual function in asymptomatic individuals carrying leber hereditary optic neuropathy mutation

Purpose: To evaluate the retinal structure and visual function in asymptomatic subjects with Leber hereditary optic neuropathy (LHON) mutation. We evaluated macular ganglion cell layer and inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (RNFL) and assessed high and low contrast visual acuity and visual field sensitivity.Methods: A total of 28 asymptomatic carriers (37±20 years), 53.5% females, were enrolled. 100% and 13% contrast visual acuity, visual field sensitivity, and Optic coherence tomography (OCT) were performed. Visual field was evaluated with Humphrey Field Analyzer 3 using SITA 24‐2 strategy with white‐on‐white size III stimuli. OCT imaging was performed with a Zeiss Cirrus 5000 HD‐OCT using macular cube 512x128 scan, and optic disc cube 200x200 scan. The thickness and visual function metrics obtained were analyzed to investigate within‐subject differences. For each subject, the eyes were divided into best and worst based on the visual function parameters and as thickest and thinnest based on the structural measurements.Results: The mean difference between best and worst eye for 100% and 13% visual acuity were 0.03 ± 0.05 (range: 0 to 0.23) and 0.05 ± 0.06 logMAR (range: 0 to 0.18) respectively. For the mean deviation from visual field measurements varied by 1.11 ± 0.85 dB (range: 0.10 to 3.19) between the eyes. The mean difference between thickest and thinnest eye for GCL+IPL and RNFL were 1.48 ± 1.45 μm (range: 0 to 6) and 3.22 ± 2.85 μm (range: 0 to 9) respectively. All the visual function metrics and the structural measurements displayed small but statistically significant inter‐eye differences (p &lt; .005).Conclusions: In asymptomatic LHON carriers inter‐eye differences were found in structural and functional measurements. OCT imaging and precise visual function test may provide useful information about disease conversion risk in asymptomatic carriers.

The retinal structure and visual function in asymptomatic individuals carrying leber hereditary optic neuropathy mutation

Purpose: To evaluate the retinal structure and visual function in asymptomatic subjects with Leber hereditary optic neuropathy (LHON) mutation. We evaluated macular ganglion cell layer and inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (RNFL) and assessed high and low contrast visual acuity and visual field sensitivity.Methods: A total of 28 asymptomatic carriers (37±20 years), 53.5% females, were enrolled. 100% and 13% contrast visual acuity, visual field sensitivity, and Optic coherence tomography (OCT) were performed. Visual field was evaluated with Humphrey Field Analyzer 3 using SITA 24‐2 strategy with white‐on‐white size III stimuli. OCT imaging was performed with a Zeiss Cirrus 5000 HD‐OCT using macular cube 512x128 scan, and optic disc cube 200x200 scan. The thickness and visual function metrics obtained were analyzed to investigate within‐subject differences. For each subject, the eyes were divided into best and worst based on the visual function parameters and as thickest and thinnest based on the structural measurements.Results: The mean difference between best and worst eye for 100% and 13% visual acuity were 0.03 ± 0.05 (range: 0 to 0.23) and 0.05 ± 0.06 logMAR (range: 0 to 0.18) respectively. For the mean deviation from visual field measurements varied by 1.11 ± 0.85 dB (range: 0.10 to 3.19) between the eyes. The mean difference between thickest and thinnest eye for GCL+IPL and RNFL were 1.48 ± 1.45 μm (range: 0 to 6) and 3.22 ± 2.85 μm (range: 0 to 9) respectively. All the visual function metrics and the structural measurements displayed small but statistically significant inter‐eye differences (p &lt; .005).Conclusions: In asymptomatic LHON carriers inter‐eye differences were found in structural and functional measurements. OCT imaging and precise visual function test may provide useful information about disease conversion risk in asymptomatic carriers.

Conditioned media from dental pulp stem cells to counteract age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract AMD towards the most severe stages characterised by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easy source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) are considered promising for regenerative medicine. The main advantage of DPSCs is related to their paracrine immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. Recent studies demonstrated the therapeutic potential of DPSCs-conditioned media (CM) in neurodegenerative diseases. In addition, we have already shown a differential expression of some growth factors and cytokines in CM derived from DPSCs cultured in hypoxia and normoxia conditions. In this study we evaluated the capability of DPSCs-CM to counteract retinal degeneration in an animal model of AMD. DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD). We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model. DPSCs-CM obtained from hypoxia (HYPO-CM) or normoxia (NORM-CM), were able to preserve the retinal function, to reduce the damaged area and to counteract the upregulation of key factors involved in retinal degeneration, like FGF-2. Furthermore, we demonstrated that neither conditioned media modified inflammatory activation, as shown by both microglia activation and GFAP upregulation, but in vitro studies demonstrated a significant effect of both CM to counteract oxidative stress, one of the main causes of AMD. Taken together, our study demonstrated that NORM-CM and HYPO-CM, albeit with a different chemical composition, could represent eligible candidates to counteract retinal degeneration in an animal model of AMD. Further studies are needed to obtain conditioned media with the best performance in term of retinal protection.

Optic nerve damage model: A preliminary study to determine injury duration and degree of gliosis

Aims/Purpose: The aim of this study was to investigate the effects of varying durations of optic nerve compression on retinal function and morphology in an adult DA/HanR rat with optic nerve crush model.Methods: In the study, adult DA/HanR rats (4‐8 mo) were divided into 5 experimental groups. Lateral canthotomy and lateral bulbar conjunctiva incision were performed to reach the area. The optic nerve was held 2‐3 mm posterior to the globe with the help of calibrated forceps and compressed for four different periods of time: 10 seconds, 15 seconds, 30 seconds and 2 minutes. During the injury, retinal fundus observation of rats was checked with a 90‐diopter fundus lens. To evaluate changes in vision after optic nerve damage, in vivo electrophysiological tests (VEP, EEG and ERG) with daylight stimulator, a light intensity of 500 μW/cm2, was studied. Changes in optic nerve and retina morphology after injury were evaluated by hematoxylin‐eosin (H&amp;E), TUNEL assay, immunofluorescence staining of gliosis and retina cell markers.Results: It was observed that the response to light was reduced in both the retina (ERG) and visual cortex (VEP‐EEG) in the damaged eyes compared to the control group. Retina cell survival showed decrease in injured groups by TUNEL assay. In immunofluorescence staining, an increase in the severity of gliosis with activation of the microglia and Müller cells in the retina and optic nerve depending on the duration of damage was shown by the expressions of GFAP, Glutamine Synthetase and Vimentin. It was observed that the expression of the neural marker NeuN and the photoreceptor marker Rhodopsin decreased upon injury.Conclusions: Our study provided preliminary results to further optic nerve regeneration studies to select optimum time points for improve axonal healing in retina and optic nerve injuries.Funding Information: This work is supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under Grant ARDEB‐121S762

All-Optically Controlled Memristive Device Based on Cu2O/TiO2 Heterostructure Toward Neuromorphic Visual System.

The optoelectronic memristor integrates the multifunctionalities of image sensing, storage, and processing, which has been considered as the leading candidate to construct novel neuromorphic visual system. In particular, memristive materials with all-optical modulation and complementary metal oxide semiconductor (CMOS) compatibility are highly desired for energy-efficient image perception. As a p-type oxide material, Cu2O exhibits outstanding theoretical photoelectric conversion efficiency and broadband photoresponse. In this work, an all-optically controlled memristor based on the Cu2O/TiO2/sodium alginate nanocomposite film is developed. Optical potentiation and depression behaviors have been implemented by utilizing visible (680 nm) and ultraviolet (350 nm) light. Furthermore, a 7 × 9 optoelectronic memristive array with satisfactory device variation and environment stability is constructed to emulate the image preprocessing function in biological retina. The random noise can be reduced effectively by utilizing bidirectional optical input. Beneficial from the image preprocessing function, the accuracy of handwritten digit classification increases more than 60%. Our work presents a pathway toward high-efficient neuromorphic visual system and promotes the development of artificial intelligence technology.