Retinal Structure Research Articles

Enhancing Late Retinopathy of Prematurity Outcomes with Fresh Bone Marrow Mononuclear Cells and Melatonin Combination Therapy.

Retinopathy of prematurity (ROP) is a vasoproliferative disease affecting premature neonates with life-lasting impacts. This study aims to investigate the long-term functional outcomes and alterations in neural retina architecture following the intravitreal transplantation of bone marrow mononuclear cells (BMMNC) in the rat models of ROP, and to evaluate the effect of adjunctive therapy with melatonin. 32 neonate rats were employed. The ROP model was developed in 10 neonatal rats, and two were assigned as control. The ROP models received BMMNC suspension, containing 1.2 × 105cells, in their right eye, and normal saline in left at p12. Five ROP rats received 12.5 mg/kg melatonin orally for five days (p12 to p17). Optical coherence tomography (OCT) and electroretinography (ERG) were performed on p47. Eyes were then harvested on p47, and after six months for histology, immunofluorescence (anti-calbindin, anti-PKC, and anti-Brn3), and immunohistochemistry (synaptophysin). Cell therapy alone and with melatonin increased retinal thickness, and improved oscillatory potentials on ERG. Combination therapy increased horizontal and retinal ganglion cell populations. All treatments improved synaptic maturity in the inner plexiform layer, but only combination therapy was effective on the outer plexiform layer. Melatonin and BMMNCs combination therapyeffectively ameliorates retinal structural and functional deficits at later ROP stages, without causing severe adverse effects.It significantly increases the survival of post-receptor retinal neurons and preserves retinal synaptic structures in the long term, highlighting the promising potential of this novel combination therapy approach to minimize visual deficits in ROP patients.

112° field of view high-resolution swept-source OCT angiography for rat retinas

This study introduces an ultra-wide field (UWF) and high-resolution swept-source optical coherence tomographic angiography (OCTA) system for rat retinal imaging. Using an asymmetrical optics design, the system achieves unprecedented details of retinal structures and vascular plexuses over a large field of view (112°) in a single-shot acquisition. Views of single-nerve fiber bundles and single capillary vessels are consistently visible over a 112° field of view. The system has a long imaging range and high penetration and allows a full view of vitreous hyaloid vessels, retina, choroid, sclera, and posterior ciliary arteries, down to sub-sclera connective tissues. In a longitudinal study of oxygen-induced retinopathy (OIR) in rats, the system successfully revealed the progression and regression of OIR-related vascular pathologies, such as ischemia, neovascularization, and tortuosity. To our knowledge, this novel UWF-OCT/OCTA prototype designed for rat retinal imaging will be a vital tool for monitoring disease progression and evaluating therapeutic interventions in preclinical models.

A Method for Retina Segmentation by Means of U-Net Network

Retinal image segmentation plays a critical role in diagnosing and monitoring ophthalmic diseases such as diabetic retinopathy and age-related macular degeneration. We propose a deep learning-based approach utilizing the U-Net network for the accurate and efficient segmentation of retinal images. U-Net, a convolutional neural network widely used for its performance in medical image segmentation, is employed to segment key retinal structures, including the optic disc and blood vessels. We evaluate the proposed model on a publicly available retinal image dataset, demonstrating interesting performance in automatic retina segmentation, thus showing the effectiveness of the proposed method. Our proposal provides a promising method for automated retinal image analysis, aiding in early disease detection and personalized treatment planning.

Blue light reflectance imaging in non-perfusion areas detection: insights from multimodal analysis

DesignA retrospective, cross-sectional image analysis using a convenience sample.SubjectsFive cases selected based on the availability of comprehensive imaging data.MethodsThis study involved a retrospective review of images from five cases, focusing on the use of retinal monochromatic blue light reflectance (BLR) imaging to detect non-perfusion areas. Two cases of sickle-cell retinopathy demonstrated peripheral retinal non-perfusion identified through widefield fluorescein angiography. Three other cases—one with branch retinal vein occlusion, one with branch retinal artery occlusion, and one presenting paracentral acute middle maculopathy showed focal macular non-perfusion detected by structural OCT and OCTA. The areas of nonperfused retinal tissue, confirmed by fluorescein angiography, OCT, and OCTA, were then correlated with findings from the BLR image. This correlation aimed to identify any potential associations between these imaging modalities.Main outcome measuresEnhance understanding of the utilization of retinal monochromatic BLR images as a non-perfusion biomarker.ResultsThe perfusion defects identified through fluorescein angiography were qualitatively correlated with hypo-reflective regions observed in the BLR images. A notable correlation was also observed between the OCTA deep capillary plexus findings and the BLR images. Additionally, areas of retinal thinning identified on structural OCT thickness maps corresponded with the hypo-reflective regions in the BLR images. This indicates the potential of BLR in identifying non-perfused retinal areas.ConclusionsThis study reinforces the evidence, through OCT, OCTA, and angiographic correlation, that the BLR can effectively identify areas of retinal non-perfusion in a non-invasive manner. Further research is warranted to assess the method’s sensitivity, specificity, and limitations. While the interaction of blue light with the retina, leading to specular reflections and scattering, is established, this research represents a pioneering effort in suggesting which specific retinal structures may be implicated in this phenomenon. This novel insight opens avenues for deeper exploration into the underlying mechanisms and potential clinical applications of utilizing the BLR imaging technique for assessing retinal vascular abnormalities.

Evaluating the effects of three anesthetic regimens on retinal structure and function in the living mouse eye using a customized bimodal OCT/ORG system

Abstract Optical coherence tomography (OCT) is a non-invasive imaging technique that generates cross-sectional images of biological tissues at millimeter-level penetration depth with micron-level resolution. In this study, we developed a custom spectral-domain OCT system equipped with a flash stimulus module for dual-modality imaging of mouse retinal structure and function. The axial resolution of the system reached ∼2.7/2 μm in air/tissue following optimization and calibration. We deployed this system to conduct in vivo OCT structural imaging and optoretinography (ORG) functional assessment of mouse retina to investigate the effects of three anesthesia regimens. Statistical analysis of the results indicates that anesthesia results in a smaller relative intensity of inner/outer segment junction and external limiting membrane and a thickening of the outer segment compared to an awake state. Meanwhile, significant differences were observed in the effects on retinal structure and function between isoflurane and tribromoethanol anesthesia, while differences between isoflurane and esketamine+xylazine groups were small. These findings suggest that the type of anesthetic should be taken into account when comparing imaging results across studies reported in the literature.

Abnormal outer and inner retina in a mouse model of Huntington’s disease with age

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities—specifically whether they originate in the inner or outer retina—remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease.

Evaluation of retinal nerve fiber layer and choroidal structure in obese children and adolescents

Aim: Obesity-related vascular damage and endothelial dysfunction have deleterious effects on the ocular vasculature. It was aimed to examine optical coherence tomography (OCT) parameters in obese and overweight children and to define their relationship with metabolic markers in this study. Methods: The patient group consisted of 26 obese, 24 overweight patients aged between 8 and 18 years. The control group consisted of 25 healthy children with normal body mass index (BMI). This was a cross-sectional observational study. Serum glucose, lipid parameters, and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated. Measurement of choroidal thickness was performed with Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA, USA). Retinal nerve fiber layer (RNFL) thickness was determined by an automatic computer algorithm without the need for user measurement. Results: There were no differences in subfoveal, nasal, temporal choroidal thickness, and RNFL between obese, overweight, and control groups (p>0.05). A positive (linear) moderate relationship was found between RNFL and the HOMA-IR of 26 patients in the obese group (r=0.389) (p=0.049). A positively weak correlation was found between height and RNFL in obese patient group (r=0.264, p=0.028). Conclusion: In the study, RNFL thickness increased as HOMA-IR level increased in obese children and adolescents. RNFL decreased as the height increased in obese children and adolescents. We believe that more comprehensive data about the effect of obesity on RNFL and choroidal thickness will be obtained with prospective studies in which the obese patient group with insulin resistance is taken separately and disease durations are defined, and long-term patient follow-up is performed.

Multi-Characteristic Opsin Therapy to Functionalize Retina, Attenuate Retinal Degeneration, and Restore Vision in Mouse Models of Retinitis Pigmentosa.

Retinal degeneration 1 and 10 (rd1 and rd10) mice are useful animal models of retinitis pigmentosa (RP) with rapidly and slowly progressive pathologies, respectively. Our study aims were to determine the effect of adeno-associated viral vector 2 (AAV2)-delivered multi-characteristic opsin (MCO-010; under the control of a metabotropic glutamate receptor-6 promoter enhancer) on the morphological and functional characteristics of vision in both rd1 and rd10 mice. Various retinal measures of MCO-010 transduction and electrophysiological, behavioral, and other routine blood analyses were performed in the rd1 and/or rd10 mice after intravitreal injection of 1µL of MCO-010 or AAV2 vehicle. Functional tests included electroretinogram, visually evoked potential, and behavior assay (optomotor and water maze). Retinal thickness, intraocular pressure, and plasma cytokine levels were also determined. Following intravitreal MCO-010 injection, approximately 80% of bipolar cells were transduced in the retina, and no alterations in retinal thickness were observed at 4months post-injection. However, retinal thickness significantly decreased in control mice. MCO-010 treatment increased head movements and induced faster navigation of mice to the platform in a water-maze test. The MCO-010 gene therapy helped preserve visually evoked electrical response in the retina and visual cortex. No ocular toxicity, immunotoxicity, or phototoxicity was observed in the MCO-010-treated mice, even under chronic intense light conditions. Intravitreal MCO-010 was well tolerated in rd1 and rd10 mice models of RP, and it appeared to attenuate retinal photoreceptor degeneration based on retinal structure and functional outcome measures. As reported here, optogenetic treatment of the inner retina attenuates further retinal degeneration in addition to photosensitizing higher order neurons, and this disease-modifying aspect should be evaluated in optogenetic clinical trials.

Splice variant of retinal G-protein-coupled receptor deletion (RGR-d)-mediated dysregulation of autophagy increases the susceptibility to age-related macular degeneration-like defects.

The splice variant of retinal G-protein-coupled receptor deletion (RGR-d) is a persistent component of drusen and may be involved in the pathogenesis of dry age-related macular degeneration (AMD). Increasing evidence has demonstrated the critical role of autophagy in AMD. In this study, we investigated whether RGR-d disrupts autophagy in early dry AMD in vivo and in vitro. Fundus imaging and fluoroscopy were performed on RGR-d mice created by multiplex gene editing. The retina microstructure was evaluated by performing hematoxylin and eosin (H&E) staining as well as transmission electron microscopy (TEM). Retinal function was assessed by full-field electroretinography (ERG). After lentivirus transfection and stimulation, the permeability, phagocytosis, and tight junctions of ARPE-19 cells were evaluated. Western blotting of ATG5, beclin-1, LC3II/I, and P62 was performed to detect the changes in autophagy pathways. Atrophy and patchy penetrating hyperfluorescent foci, consistent with early AMD-like defects, were observed in the fundus of 12-month-old RGR-d mice. H&E staining of retinal tissues indicated thinning of each layer of the retinal structure. H&E staining of retinal tissues indicated thinning of each layer of the retinal structure. TEM analysis showed some diffuse granular deposits. And the morphology of choroidal microvascular endothelial cells was degraded and distorted. The morphology of the photoreceptor outer segments showed structural damage and Bruch's membrane was thickened. ERG indicated that the photoreceptor of RGR-d mice were dysfunctional. Changes in autophagy-related protein expression were observed in the retinal pigment epithelium and retinal neuroepithelium, and autophagy regulation was decreased. Palmitic acid (PA) stimulation caused permeability, phagocytosis, and tight junction dysfunction in cells overexpressing RGR-d. Beclin-1 and LC3II/I expression levels were significantly decreased and that of P62 was elevated in RGR-d cells after PA stimulation. RGR-d disrupts the autophagy pathway, causing the development of an early AMD-like pathophysiology.

IL-33 protects retinal structure and function via mTOR/S6 signaling pathway in optic nerve crush

This study demonstrated the functions and molecular mechanisms of the IL-33/ST2 axis in experimental optic neuropathy. C57BL/6J mice were used to establish an optic nerve crush (ONC) model. ONC mice were administered with IL-33 intraperitoneal injection, with PBS vehicle as control. Immunofluorescence, quantitative RT-PCR, and western blot techniques were utilized to assess the expression of the IL-33/ST2 axis. The electroretinography (ERG), optical coherence tomography (OCT), H&E, and luxol fast blue were used to assess the structural and functional changes. Western blot was employed to detect the activation of the mTOR/S6 pathway. The IL-33 expression level in the inner nuclear layer of the retina in ONC mice reached its peak on day 3, accompanied by a significant increase in IL-33 receptor ST2 expression. IL-33 treatment promoted the survival of retinal ganglion cells, restored the thickness of inner retina layer (IRL), alleviated the demyelination of the optic nerve, and recovered the decreased amplitude of b-wave in ONC mice. Furthermore, administration of IL-33 activated the mTOR/S6 signaling pathway in RGCs, which was significantly suppressed in the ONC condition. This study indicated that boosting the IL-33/ST2/mTOR/S6 pathway can protect against structural and functional damage to the retina and optic nerve induced by ONC. As a result, the IL-33/ST2 axis holds potential as a therapeutic option for treating various optic neuropathies.

Multimodal photoacoustic microscopy and optical coherence tomography ocular biomarker imaging in Alzheimer's disease in mice

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid beta (Aβ)-containing extracellular plaques and tau-containing intracellular neurofibrillary tangles. Reliable and more accessible biomarkers along with associated imaging methods are essential for early diagnosis and to develop effective therapeutic interventions. Described here is an integrated photoacoustic microscopy (PAM) and optical coherence tomography (OCT) dual-modality imaging system for multiple ocular biomarker imaging in an AD mouse model. Anti-Aβ-conjugated Au nanochains (AuNCs) were engineered and administered to the mice to provide molecular contrast of Aβ. The retinal vasculature structure and Aβ deposition in AD mice and wild-type (WT) mice were imaged simultaneously by dual-wavelength PAM. OCT distinguished significant differences in retinal layer thickness between AD and WT animals. With the unique ability of imaging the multiple ocular biomarkers via a coaxial multimodality imaging system, the proposed system provides a new tool for investigating the progression of AD in animal models, which could contribute to preclinical studies of AD.

Adaptive optics scanning laser ophthalmoscopy in a heterogenous cohort with Stargardt disease

Image based cell-specific biomarkers will play an important role in monitoring treatment outcomes of novel therapies in patients with Stargardt (STGD1) disease and may provide information on the exact mechanism of retinal degeneration. This study reports retinal image features from conventional clinical imaging and from corresponding high-resolution imaging with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) in a heterogenous cohort of patients with Stargardt (STGD1) disease. This is a prospective observational study in which 16 participants with clinically and molecularly confirmed STGD1, and 7 healthy controls underwent clinical assessment and confocal AOSLO imaging. Clinical assessment included short-wavelength and near-infrared fundus autofluorescence, spectral-domain optical coherence tomography, and macular microperimetry. AOSLO images were acquired over a range of retinal eccentricities (0°–20°) and mapped to areas of interest from the clinical images. A regular photoreceptor mosaic was identified in areas of normal or near normal retinal structure on clinical images. Where clinical imaging indicated areas of retinal degeneration, the photoreceptor mosaic was disorganised and lacked unambiguous cones. Discrete hyper-reflective foci were identified in 9 participants with STGD1 within areas of retinal degeneration. A continuous RPE cell mosaic at the fovea was identified in one participant with an optical gap phenotype. The clinical heterogeneity observed in STGD1 is reflected in the findings on confocal AOSLO imaging.

Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion.

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

In vivo volumetric analysis of retinal vascular hemodynamics in mice with spatio-temporal optical coherence tomography.

Microcirculation and neurovascular coupling are important parameters to study in neurological and neuro-ophthalmic conditions. As the retina shares many similarities with the cerebral cortex and is optically accessible, a special focus is directed to assessing the chorioretinal structure, microvasculature, and hemodynamics of mice, a vital animal model for vision and neuroscience research. We aim to introduce an optical imaging tool enabling in vivo volumetric mouse retinal monitoring of vascular hemodynamics with high temporal resolution. We translated the spatio-temporal optical coherence tomography (STOC-T) technique into the field of small animal imaging by designing a new optical system that could compensate for the mouse eye refractive error. We also developed post-processing algorithms, notably for the assessment of (i) localized hemodynamics from the analysis of pulse wave-induced Doppler artifact modulation and (ii) retinal tissue displacement from phase-sensitive measurements. We acquired high-quality, in vivo volumetric mouse retina images at a rate of 113Hz over a lateral field of view of . We presented high-resolution en face images of the retinal and choroidal structure and microvasculature from various layers, after digital aberration correction. We were able to measure the pulse wave velocity in capillaries of the outer plexiform layer with a mean speed of 0.35mm/s and identified venous and arterial pulsation frequency and phase delay. We quantified the modulation amplitudes of tissue displacement near major vessels (with peaks of 150nm), potentially carrying information about the biomechanical properties of the retinal layers involved. Last, we identified the delays between retinal displacements due to the passing of venous and arterial pulse waves. The developed STOC-T system provides insights into the hemodynamics of the mouse retina and choroid that could be beneficial in the study of neurovascular coupling and vasculature and flow speed anomalies in neurological and neuro-ophthalmic conditions.

Retinal Function in Young Adults Following Topical Application of Levodopa to the Eye.

Levodopa has been investigated as a therapeutic solution for ocular disorders involving dysregulation of the dopaminergic system, especially in the context of myopia. However, given the critical role dopamine plays in normal vision, this phase I trial examined whether levodopa/carbidopa eye drops induce any regional changes in retinal structure and function. Twenty-nine healthy male subjects 18 to 30 years of age were randomly assigned to receive either a low (1.4/0.34 µmoles/day, n = 14) or high (2.7/0.68 µmoles/day, n = 15) dose of levodopa/carbidopa eye drops in 1 eye for 28 consecutive days. A placebo solution was applied to all fellow eyes. Measures included visual acuity, regional frequency doubling perimetry, regional multifocal electroretinogram (mfERG) and optical coherence tomography (retinal thickness). Outcome measures were undertaken at baseline, end-of-treatment (4 weeks), and at a follow-up (4 months post-treatment). For low dose treated eyes, regional analysis showed a small, statistically significant change in mfERG recordings (increase in ring 5 amplitude in low dose treated eyes, P < 0.05) and the retinal thickness map (localized retinal thinning in low dose treated eyes, P < 0.05). These changes were not clinically significant. No significant changes were observed in high dose treated eyes. Pharmacokinetic analysis (rabbits) demonstrated that levodopa was not detectable within blood and peaked within the eye at 15 to 30 minutes (and eliminated within 4 hours). No clinically significant effects of levodopa/carbidopa eye drops were found with regard to normal retinal structure and function following short-term use. This study further demonstrates the safety of topical levodopa, which may support its use in the treatment of ocular disorders in which the dopamine system is dysregulated.

CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments.

Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for retinal homeostasis. Dysregulation of the phagocytotic process is associated with irreversible retinal degenerative diseases. However, the molecular mechanisms underlying the phagocytic activity of RPE cells remain elusive. In an effort to uncover proteins orchestrating retinal function, the cylindromatosis (CYLD) deubiquitinase is identified as a critical regulator of photoreceptor outer segment phagocytosis. CYLD-deficient mice exhibit abnormal retinal structure and function. Mechanistically, CYLD interacts with enkurin domain containing protein 1 (ENKD1) and deubiquitinates ENKD1 at lysine residues K141 and K242. Deubiquitinated ENKD1 interacts with Ezrin, a membrane-cytoskeleton linker, and stimulates the microvillar localization of Ezrin, which is essential for the phagocytic activity of RPE cells. These findings thus reveal a crucial role for the CYLD-ENKD1-Ezrin axis in regulating retinal homeostasis and may have important implications for the prevention and treatment of retinal degenerative diseases.

Bacteriophage Therapy for Staphylococcus aureus Induced Postoperative Acute Endophthalmitis In Vivo

Background: Postoperative acute endophthalmitis is a rare but severe complication following cataract surgery, with bacterial pathogens such as Staphylococcus aureus being the leading cause. Despite declining incidence rates globally, visual outcomes remain poor in many cases. Recent studies have explored the potential of bacteriophage therapy to treat bacterial infections, particularly for antimicrobial-resistant strains. This study aimed to assess the therapeutic effectiveness of bacteriophage treatment in a rabbit model of S. aureus-induced acute postoperative endophthalmitis. Methods: The study employed a randomized, controlled, posttest-only design using New Zealand white rabbits. Following extracapsular lens extraction surgery, rabbits were injected with S. aureus intracamerally to induce endophthalmitis. The treatment group received additional bacteriophage therapy. Ocular inflammation was assessed by measuring two biomarkers, myeloperoxidase (MPO) and intercellular adhesion molecule-1 (ICAM-1), using enzyme-linked immunosorbent assay (ELISA) from vitreous fluid samples. Histopathological analysis of retinal and scleral structures was performed post-enucleation. Statistical analyses were conducted using independent t-tests. Results: The treatment group showed significantly lower ICAM-1 levels (p &lt; 0.001), indicating reduced leukocyte infiltration and inflammation compared to the control group. MPO levels were slightly elevated in the treatment group but were not statistically significant (p = 0.261). Histopathological examination revealed that retinal structures in the treatment group were preserved with reduced inflammatory cell infiltration, whereas the control group displayed extensive retinal damage, including neovascularization and retinal detachment. Conclusion: Bacteriophage therapy significantly reduced ocular inflammation and tissue damage in S. aureus-induced endophthalmitis, as evidenced by lower ICAM-1 levels and better-preserved retinal structures in the treatment group. These findings suggest that bacteriophage therapy may be an effective alternative to conventional treatments for postoperative acute endophthalmitis, particularly in cases involving antibiotic-resistant bacteria. Further studies are warranted to explore its broader clinical applicability.

Impact of transcranial Direct Current Stimulation on stereoscopic vision and retinal structure in adult amblyopic rodents.

The impact of visual deprivation on retinal structure is widely debated. Experimental models, like monocular deprivation through lid suture, provide insights into the consequences of lacking visual experience during development. This deprivation delays primary visual cortex (CV1) maturation due to improper neural connection consolidation, which remains plastic beyond the critical period. However, few studies have used Optical Coherence Tomography (OCT) to investigate structural alterations in the retina of animal models following monocular deprivation. Instead, some studies have focused on the ganglion cell layer using post-mortem histological techniques in amblyopia models induced by monocular deprivation. In this study, we used Cliff test to assess stereoscopic vision and spectral domain optical coherence tomography (SD-OCT) to evaluate retinal changes in an in vivo model of visual deprivation treated with Transcranial Direct Current Stimulation (tDCS). The depth perception test initially revealed differences between individuals with amblyopia and the control group. However, after 8 tDCS sessions, amblyopic subjects matched the control group's performance, which remained stable Additionally, significant changes were observed in retinal structures post-tDCS treatment. Specifically, the thickness of the Nerve Fiber Layer + Ganglion Cell Layer + Inner Plexiform Layer (NFL+GCL+IPL) increased significantly in amblyopic eyes (p<0.001). Moreover, significant retinal thickening, including the Nerve Fiber Layer + Ganglion Cell Layer + Inner Plexiform Layer (NFL+GCL+IPL) and the entire retina, was observed post-tDCS treatment (p<0.05), highlighting the critical role of tDCS in ameliorating amblyopia. Additionally, treated animals exhibited reduced thickness in the Inner Nuclear Layer (INL) and Outer Nuclear Layer (ONL). tDCS treatment effectively restores amblyopic individuals' stereoscopic vision, aligning their performance with controls, while impacting retinal structure, highlighting its potential in ameliorating amblyopia's visual deficits.

Regeneration of zebrafish retina following toxic injury

The structure of the zebrafish retina appears to be very similar to that of mammals, that is why it is used as a model for studying the eye. Indeed, the zebrafish retina can regenerate itself through mechanisms of Müller cell reprogramming. In this research, adult zebrafish were exposed to aluminum to cause damage in the retina and thus evaluate the regenerative capacity of the damaged tissue. Histological and histochemical analyses assessed the retinal structure and the neurodegenerative process, respectively. An expression analysis of PARPs was carried out to verify whether a potential oxidative DNA damage happens. In addition, some genes involved in the regeneration process (pax6a, pax2a, ngn1, and notch1a) were analyzed. The data confirmed the toxicity of aluminum which caused retinal neurodegeneration, but also highlighted the ability of zebrafish to regenerate the retinal structure, repairing the damage and confirming its use as a good model for translational studies.