Retinal Degenerative Changes Research Articles

Histomorphology and Histomorphometrics of the retina in Juvenile and Adult African Giant Rats (Cricetomys gambianus)

Aging is accompanied with various forms of functional ultrastructural and morphological changes in the eye, including the retina, leading to vision deterioration. However, age related retinal degenerative changes requires further elucidation especially as all previous studies on age-related change of the retina were done in mutant mouse strain models of hereditary retinal degenerations. The potential of using African giant rats (AGRs) as models for ageing in the eye, especially retina, was explored in this study. A total of 14 AGRs divided into two age groups (juvenile and adult) were used to study the histomorphology and histomorphometrics of the retina as well as retinal astrocyte morphology and heterogeneity. Histological findings included retinal atrophy and hypoplasia, with cellular swellings of neuronal cell populations and astrocytes soma and ramifications in the retina of adult compared to juvenile AGR. We suggest that AGR be used as animal model for translational research into normal aging process of the retina, as well as to elucidate the process of age-related neuronal cells loss.

Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood–retinal barrier damages and disease susceptibilities

BackgroundThe association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood–retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases.ObjectivesTo describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities.MethodsA PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage.ResultsAcute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation.ConclusionThis study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation.Graphical abstract

Multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence imaging of USH2A knockout rabbits

Usher syndrome type 2A (USH2A) is a genetic disorder characterized by retinal degeneration and hearing loss. To better understand the pathogenesis and progression of this syndrome, animal models such as USH2A knockout (USH2AKO) rabbits have been developed. In this study, we employed multimodal imaging techniques, including photoacoustic microscopy (PAM), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA) imaging to evaluate the retinal changes in the USH2AKO rabbit model. Twelve New Zealand White rabbits including USH2AKO and wild type (WT) were used for the experiments. Multimodal imaging was implemented at different time points over a period of 12 months to visualize the progression of retinal changes in USH2AKO rabbits. The results demonstrate that ellipsoid zone (EZ) disruption and degeneration, key features of Usher syndrome, began at the age of 4 months old and persisted up to 12 months. The EZ degeneration areas were clearly observed on the FAF and OCT images. The FAF images revealed retinal pigment epithelium (RPE) degeneration, confirming the presence of the disease phenotype in the USH2AKO rabbits. In addition, PAM images provided high-resolution and high image contrast of the optic nerve and the retinal microvasculature, including retinal vessels, choroidal vessels, and capillaries in three-dimensions. The quantification of EZ fluorescent intensity using FAF and EZ thickness using OCT provided comprehensive quantitative data on the progression of degenerative changes over time. This multimodal imaging approach allowed for a comprehensive and non-invasive assessment of retinal structure, microvasculature, and degenerative changes in the USH2AKO rabbit model. The combination of PAM, OCT, and fluorescent imaging facilitated longitudinal monitoring of disease progression and provided valuable insights into the pathophysiology of USH2A syndrome. These findings contribute to the understanding of USH2A syndrome and may have implications for the development of diagnostic and therapeutic strategies for affected individuals. The multimodal imaging techniques employed in this study offer a promising platform for preclinical evaluation of potential treatments and may pave the way for future clinical applications in patients with Usher syndrome.

Retinopathy as an initial sign of hereditary immunological diseases: report of six families and challenges in eye clinic.

Retinal degenerative or inflammatory changes may occur with hereditary immunological disorders (HID) due to variants in approximately 20 genes. This study aimed to investigate if such retinopathy may present as an initial sign of immunological disorders in eye clinic. The variants in the 20 genes were selected from in-house exome sequencing data from 10,530 individuals with different eye conditions. Potential pathogenic variants were assessed by multistep bioinformatic analysis. Pathogenic variants were defined according to the ACMG/AMP criteria and confirmed by Sanger sequencing, co-segregation analysis, and consistency with related phenotypes. Ocular clinical data were thoroughly reviewed, especially fundus changes. A total of seven pathogenic variants in four of the 20 genes were detected in six probands from six families, including three with hemizygous nonsense variants p.(Q308*), p.(Q416*), and p.(R550*) in MSN, one with homozygous nonsense variants p.(R257*) in AIRE, one with compound heterozygous nonsense variants p.(R176*) and p.(T902*) in LAMB2, and one with a known c.1222T>C (p.W408R) heterozygous variant in CBL. Ocular presentation, as the initial signs of the diseases, was mainly retinopathy mimicking other forms of hereditary retinal degeneration, including exudative vitreoretinopathy in the three patients with MSN variants or tapetoretinal degeneration in the other three patients. Neither extraocular symptoms nor extraocular manifestations were recorded at the time of visit to our eye clinic. However, of the 19 families in the literature with retinopathy caused by variants in these four genes, only one family with an AIRE homozygous variant had retinopathy as an initial symptom, while the other 18 families had systemic abnormalities that preceded retinopathy. This study, for the first time, identified six unrelated patients with retinopathy as their initial and only presenting sign of HID, contrary to the previous reports where retinopathy was the accompanying sign of systemic HID. Recognizing such phenotype of HID may facilitate the clinical care of these patients. Follow-up visits to such patients and additional studies are expected to validate and confirm our findings.

Automatic diagnosis of diabetic retinopathy using vision transformer based on wide-field optical coherence tomography angiography

Diabetic retinopathy (DR) is one of the major causes of visual impairment in adults with diabetes. Optical coherence tomography angiography (OCTA) is nowadays widely used as the golden criterion for diagnosing DR. Recently, wide-field OCTA (WF-OCTA) provided more abundant information including that of the peripheral retinal degenerative changes and it can contribute in accurately diagnosing DR. The need for an automatic DR diagnostic system based on WF-OCTA pictures attracts more and more attention due to the large diabetic population and the prevalence of retinopathy cases. In this study, automatic diagnosis of DR using vision transformer was performed using WF-OCTA images (12[Formula: see text]mm × 12[Formula: see text]mm single-scan) centered on the fovea as the dataset. WF-OCTA images were automatically classified into four classes: No DR, mild nonproliferative diabetic retinopathy (NPDR), moderate to severe NPDR, and proliferative diabetic retinopathy (PDR). The proposed method for detecting DR on the test set achieves accuracy of 99.55%, sensitivity of 99.49%, and specificity of 99.57%. The accuracy of the method for DR staging reaches up to 99.20%, which has been proven to be higher than that attained by classical convolutional neural network models. Results show that the automatic diagnosis of DR based on vision transformer and WF-OCTA pictures is more effective for detecting and staging DR.

CERKL-Associated Retinal Dystrophy: Genetics, Phenotype, and Natural History

To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. Multicenter retrospective cohort study. Forty-seven patients (37 families) with likely disease-causing CERKL variants. Review of clinical notes, ophthalmic images, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, and characteristics were evaluated and correlated. The mean age at the first visit was 29.6± 13.9 years, and the mean follow-up time was 9.1± 7.4 years. The most frequent initial symptom was central vision loss (40%), and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy-seven percent of the participants had double-null genotypes, and 64% had electrophysiological assessment. Among the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in ≥ 1 eye during the first 5 years of follow-up. The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma.

Sphingosine-1-phosphate receptor (S1PR) signaling regulates diverse pathophysiological processes in the central nervous system. The role of S1PR signaling in neurodegenerative conditions is still largely unidentified. Siponimod is a specific modulator of S1P1 and S1P5 receptors, an immunosuppressant drug for managing secondary progressive multiple sclerosis. We investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate excitotoxicity. Neuronal-specific deletion of sphingosine-1-phosphate receptor (S1PR1) was carried out by expressing AAV-PHP.eB-Cre recombinase under Syn1 promoter in S1PR1flox/flox mice to define the role of S1PR1 in neurons. Inner retinal electrophysiological responses, along with histological and immunofluorescence analysis of the retina and optic nerve tissues, indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury models. Further, siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve injury. Siponimod treatment also reduced microglial activation and reactive gliosis along the visual pathway. Our results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the brain. Neuronal-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of siponimod. In summary, our data demonstrated that S1PR1 signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma, and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory effects. Our findings suggest that neuronal S1PR1 is a neuroprotective therapeutic target and its modulation by siponimod has positive implications in glaucoma conditions.

Comprehensive Foveal Avascular Zone and Retinal Evaluation with Their Correlation to Visual Acuity and Glycemic Control in Diabetics Without Macular Edema

<i>Background: </i>Evaluating Foveal avascular zone by OCTA (Optical Coherence Tomography angiography) in diabetic patients, has a crucial role in early detection of pathophhsiological changes affecting the macular area, and has a pedective value for early retinal neuro degenerative changes. <i>Materials and experiments: Aim</i>: To evaluate dimensions of Foveal Avascular Zone (FAZ) at level of superficial and deep capillary plexuses (SCP/DCP) in patients with different grades of non proliferative diabetic retinopathy without Diabetic Macular Edema (DME) using OCTA. Eighty type II diabetes mellitus patients and 20 healthy control, ecxluding proliferative diabetic retinopathy and DME. Divided to four groups according to ETDRS Classification. All undewent: measurement of glycosylated hemoglobin level, standard Structural OCT for the macula and optic nerve head with OCTA for evaluation of FAZ in both SCP and DCP networks of all eyes using (Heidelberg engineering, OCT spectralis, Germany) (SD-OCT). <i>Results</i>: Mean FAZ in SCP in control group (0.32 ± 0.12) mm² versus (0.44 ± 0.17) mm² in patients` group, while FAZ IN DCP (0.23) mm² ± 0.12 in controls versus (0.34 ± 0.16) mm² in patients. There was a statistically significant wider FAZ in DR patients (P-value 0.003). <i>Conclusion</i>: Enlargement of FAZ in SCP and DCP in patients with moderate to severe NPDR without DME was detected using OCTA, Preceeded by reduction in thickness of ORL and GCC layer. This can be used to monitor the progression of the disease and to evaluate the response to treatment.

Assessing the Efficacy of Low-Dose Topical Atropine (0.01%) for Controlling the Progress of Myopia among School Children

Background: It is one of the most common abnormalities of human eyes and its incidence has dramatically risen in incidence in the last few decades. Myopia may lead to irreversible vision loss. A number of studies reflect on the effectiveness of low concentration atropine in controlling myopia. Atropine is used topically as a cycloplegic for the accommodation reflex and as a mydriatic for pupillary dilatation. Since myopia is leading cause of diminution of vision in early childhood, use of atropine (0.01%) in early stages can provide regression in myopic changes in eye. This study aimed to assess the change in spherical equivalent, changes in axial and keratometry values and retinal degenerative changes in cases of myopia treated with low dose atropine.&#x0D; Methodology: The enrolled cases of myopia will undergo thorough ophthalmological examination and will be randomized into intervention and control groups. All cases in intervention group will be treated with low dose atropine (0.01%) eye drops at night and will be followed up every 6 months for examination. The control group will be provided refractive spectacles and also followed up every 6 months. The data from both groups will be compared and analysed.&#x0D; Expected Results: Significant reduction in the progression of Myopia among school going children is expected with administration of 0.01% atropine eye drops.&#x0D; Conclusion: Use of atropine (0.01%) in early stages can provide regression in myopic changes in eye.

Modulation of SOD3 Levels Is Detrimental to Retinal Homeostasis.

Retinal oxidative stress is a common secondary feature of many retinal diseases. Though it may not be the initial insult, it is a major contributor to the pathogenesis of highly prevalent retinal dystrophic diseases like macular degeneration, diabetic retinopathy, and retinitis pigmentosa. We explored the role of superoxide dismutase 3 (SOD3) in retinal homeostasis since SOD3 protects the extracellular matrix (ECM) from oxidative injury. We show that SOD3 is mainly extracellularly localized and is upregulated as a result of environmental and pathogenic stress. Ablation of SOD3 resulted in reduced functional electroretinographic responses and number of photoreceptors, which is exacerbated with age. By contrast, overexpression showed increased electroretinographic responses and increased number of photoreceptors at young ages, but appears deleterious as the animal ages, as determined from the associated functional decline. Our exploration shows that SOD3 is vital to retinal homeostasis but its levels are tightly regulated. This suggests that SOD3 augmentation to combat oxidative stress during retinal degenerative changes may only be effective in the short-term.

Retinitis pigmentosa is associated with shifts in the gut microbiome

The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice. In rd10 mice, retinal responsiveness to flashlight stimuli and visual acuity were deteriorated with respect to observed in age-matched control mice. This functional decline in dystrophic animals was accompanied by photoreceptor loss, morphologic anomalies in photoreceptor cells and retinal reactive gliosis. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. Remarkably, four fairly common ASV in healthy gut microbiome belonging to Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp. were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with RP. The results indicate that retinal degenerative changes in RP are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.

Morphology of outer retinal tubulations in the outcome of exudative age-related macular degeneration according to optical coherence tomography angiography

To investigate the evolution of ORT in patients with exudative and disciform-stage CNV. The retrospective study included 340 patients with AMD, among them 235 (69%) women and 105 (31%) men with mean age of 76±7.4 years; in all, the analysis involved 267 eyes with dry AMD and 174 eyes with CNV: 92 eyes - with exudative AMD, 82 eyes - with disciform-stage disease). In addition to standard OCT, all patients underwent OCT-angiography (OCTA). In 10 cases, patients with exudative AMD were followed up after intravitreal injections of Aflibercept. ORTs were detected in 37 eyes of 32 patients (26%), all of them with CNV: 13 eyes with exudative AMD (group 1) and 24 eyes with disciform scar (group 2; p=0.013). Outer retinal tubulations are more common in the later stages of AMD, being an indicator of a deep destructive process in photoreceptors. In exudative AMD, ORTs serve as a predictive marker for poor functional outcomes.

Retinal inhibition of glycogen synthase kinase 3 beta protects against tau phosphorylation and stabilises microtubule assembly

AbstractBackgroundThe microtubule associated protein tau is known to have several important functions like assembly and stabilisation of microtubules, axonal transport and neurite outgrowth in neurodegenerative diseases. Gsk3β, glycogen synthase kinase, plays a key role in regulating tau protein activity. There is little understanding of tau and Gsk3β association in the neurogenerative disorders affecting retina. Shp2, the mitogenic phosphatase, is associated with regulation of growth factor signalling pathways in the central nervous system. In this study we demonstrate that Gsk3β inhibition can suppress tau hyperphosphorylation and rescue the inner retinal degenerative changes induced by Shp2 overexpression (OE).MethodsAdult Sprague‐Dawley rats were subjected to intravitreal injection of adeno‐associated viral vector (AAV2) overexpressing either Shp2 or eGFP alone (3.4x1012 GC/ml; n=8). These animals were also subjected to weekly (8 weeks) intravitreal injections of Gsk3β inhibitor (10 nM) and control. Electrophysiology and positive scotopic threshold response (pSTR) (‐4.3 log cd s/m2) were measured using Phoenix Ganzfield two months following intra‐ocular injections. The amplitude of each component was measured and analysed. Immunohistochemistry (IHC) and Western blot (WB) were performed for pTau Ser404, Tau, pGsk3β Ser9, Gsk3β, Ac‐tubulin and Tyr‐tubulin.ResultsShp2OE in the rat eye significantly reduced the pSTR amplitudes (44%±3.1%) compared to PBS and GFP control. However, animals treated with Gsk3β inhibitor in Shp2OE retina demonstrated significant protection of pSTR amplitudes (81±5 % protection; n=32, p&lt;0.05). IHC analysis demonstrated increased pTau Ser404 and decreased pGsk3β Ser9 immunoreactivity in the Shp2OE RGCs whereas pharmacological inhibition of Gsk3β for 8 weeks reversed the phosphorylation status of tau and Gsk3β in animals recieving AAV‐Shp2. We found that Shp2OE led to a markedly reduced expression of Ac‐tubulin (stable microtubules) and increased expression of Tyr‐tubulin (unstable microtubules) compared with control retina. Remarkably, the effects of Shp2OE on microtubules assembly was reversed upon Gsk3β inhibitor administration.ConclusionShp2OE in the retina led to abnormal tau hyperphosphorylation via Gsk3β activation causing deficits in RGCs visual function through the disruption of microtubular assembly. Shp2 may thus be an attractive therapeutic target to counter RGC neurodegeneration by reducing tau hyperphosphorylation in Alzheimer’s disease.

Retinal Detachments Related to Pathological Myopia

High myopia or pathological myopia is associated with globe elongation and a refractive error of at least -6.0 diopters (D) and/or axial length of greater than 25.5 mm. Excessive axial elongation of the globe in high myopia can cause mechanical stretching and thinning of the choroid and retinal pigment epithelium layers, resulting in various retinal degenerative changes. It is well known that individuals with pathological myopia have increased risks of retinal complications such as peripheral retinal degenerations, retinal tears, and retinal detachment. This article will review these complications and discuss the current concepts relating to these complications.

Retinal Detachment Related With Hereditary Retinal Diseases; Risk Factors, Pathogenesis and Clinical Management

Hereditary retinal disease (HRD) is a group of pathologies characterized by histologically abnormally developing vitreous gel associated with peripheral retinal degenerative or proliferative changes. In HRD alterations in the structure of the vitreous with abnormal vitreoretinal adhesions can predispose to developing Retinal Detachment (RD). Many HRD is seen with a part of syndromes most of which have systemic abnormalities affecting the joints, skeletal system, and cardiovascular system. Due to delayed diagnosis in younger age patients, without prominent symptoms, most patients with HR presented with proliferative vitreoretinopathy PVR and macula-involving RD.

Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy.

Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.

Persistent Activation of STAT3 Pathway in theRetina Induced Vision Impairment and Retinal Degenerative Changes in Ageing Mice.

Neurotrophic factors can promote the survival of degenerating retinal cells through the activation of STAT3 pathway. Thus, augmenting STAT3 activation in the retina has been proposed as potential therapy for retinal dystrophies. On the other hand, aberrant activation of STAT3 pathway is oncogenic and implicated in diverse human diseases. Furthermore, the STAT3/SOCS3 axis has been shown to induce the degradation of rhodopsin during retinal inflammation. In this study, we generated and used mice with constitutive activation of STAT3 pathway in the retina to evaluate the safety and consequences of enhancing STAT3 activities in the retina as a potential treatment for retinal degenerative diseases. We show that long-term activation of the STAT3 pathway can induce retinal degenerative changes and also exacerbate uveitis and other intraocular inflammatory diseases. Mechanisms underlying the development of vision impairment in the STAT3c-Tg mice derived in part from STAT3-mediated inhibition of rhodopsin and overexpression of SOCS3 in the retina. These results suggest that much caution should be exercised in the use of STAT3 augmentation therapy for retinal dystrophies.

The Effect of Zinc-Deficient Pregnant Albino Rats on the Retinal Development of their Embryos and Offspring: Light Microscopic and Immunohistochemical Study

AbstractBackground: Zinc is involved in many biochemical func-tions. Over 300 enzymes require zinc for their activation and nearly 2000 transcription factors require zinc for gene expres-sion. Zinc is also an effective antioxidant and anti-inflammatory agent. Nutritional deficiency of zinc may affect nearly 2 billion subjects in the developing world.Aim of Study: Because of the prevalence of malnutrition throughout the world this study was carried out to detect the possible effects of zinc-deficient pregnant albino rats on the retinal development of their embryos and offspring.Material and Methods: Female rats after mating were randomly divided into 2 equal groups: One control group received single intraperitoneal injection of distilled water on day 9 of gestation and one experimental group received intraperitoneal injections of 1.10 phenanthroline (zinc chelator purchased from Sigma Company), in a single dose of 30 mg/kg on day 9 of gestation. From the embryos and offspring of both control and treated mothers (at the following prenatal gestational days: 13, 15, 17, 19 and the following postnatal days: (newborn, 7 days, 15 days and 21 days), retinal specimens were processed for Haematoxylin & Eosin staining technique and immunohistochemical study using caspase-3 antibody was used to detect apoptosis in the postnatal age groups.Results: The light microscopic study of the 13 days zinc deficient embryo retina showed apparent shrinkage of the lens vesicle and the optic cup was well formed but it appeared to be shrunken. The retinal pigment epithelium (RPE) of 15th, 17th and 19th day old zinc-deficient embryos consistently contained apoptotic cells with vacuolated cytoplasm and rarified nuclei. The neuroblastic layer showed apparent de-crease in thickness and less mitotic features. The ganglion cell layer revealed numerous deeply stained pyknotic nuclei in the 19th gestational day. Retinae of the newborn, 7 days, 15 days, 21 days-old zinc deficient albino rats showed that the (RPE) contained some vacuolated cells with pyknotic nuclei. The organization of the retina was altered in zinc deficient rats. In addition, apparent reduction in the total retinal thickness and degenerative changes in some layers were observed. By the immunohistochemical study, there was intense positive caspase-3 reaction in all layers of the treated rat retina.Conclusion: This study revealed that zinc has a role in the developing rat retina and its deficiency causes cytoarchi-tectural and maturational changes in the retina of the albino rats. These histological changes may impair the visual functions of the retina; so it is recommended that further investigations should be carried out to determine the relevancy of deprivation of zinc as an etiologic factor in the development of retinal degeneration.

Ocular Manifestations of Alzheimer's and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer's Disease.

Dementia, including Alzheimer's disease (AD), is a major disorder, leading to several ocular manifestations amongst the elderly population. These visual disorders may be due to retinal nerve degenerative changes, including nerve fibre layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. There is no cure for Alzheimer's, but medicines can slow down the development of many of the classic symptoms, such as loss of memory and communication skills, mood swings, and depression. The disease diagnosis is difficult, and it is only possible through PET scans of the brain, detecting evidence of the accumulation of amyloid and tau. PET is expensive and invasive, requiring the injection of radioactive tracers, which bind with these proteins and glow during scanning. Recently, scientists developed promising eye-scan techniques that may detect Alzheimer's disease at its earliest stage, before major symptoms appear, leading to improved management of the disease symptoms. In this review, we are discussing the visual abnormalities of Alzheimer's and other neurodegenerative diseases, focused on ocular functional-visual-structural biomarkers, retinal pathology, and potential novel diagnostic tools.

Microglia Activation and Immunomodulatory Therapies for Retinal Degenerations.

A chronic pro-inflammatory environment is a hallmark of retinal degenerative diseases and neurological disorders that affect vision. Inflammatory responses during retinal pathophysiology are orchestrated by microglial cells which constitute the resident immune cell population. Following activation, microglia cells lose their ramified protrusions, proliferate and rapidly migrate to the damaged areas and resolve tissue damage. However, sustained presence of tissue stress primes microglia to become overreactive and results in the excessive production of pro-inflammatory mediators that favor retinal degenerative changes. Consequently, interventions aimed at overriding microglial pro-inflammatory and pro-oxidative properties may attenuate photoreceptor demise and preserve retinal integrity. We highlight the positive effects of ligands for the translocator protein 18 kDa (TSPO) and the cytokine interferon beta (IFN-β) in modulating microgliosis during retinal pathologies and discuss their plausible mechanisms of action.