Human RGR Gene and Associated Features of Age-Related Macular Degeneration in Models of Retina-Choriocapillaris Atrophy.

Age-related macular degeneration (AMD) is a progressive eye disease and the most common cause of blindness among the elderly. AMD is characterized by early atrophy of the choriocapillaris and retinal pigment epithelium (RPE). Although AMD is a multifactorial disease with many environmental and genetic risk factors, a hallmark of the disease is the origination of extracellular deposits, or drusen, between the RPE and Bruch membrane. Human retinal G-protein-coupled receptor (RGR) gene generates an exon-skipping splice variant of RGR-opsin (RGR-d; NP_001012740) that is a persistent component of small and large drusen. Herein, the findings show that abnormal RGR proteins, including RGR-d, are pathogenic in an animal retina with degeneration of the choriocapillaris, RPE, and photoreceptors. A frameshift truncating mutation resulted in severe retinal degeneration with a continuous band of basal deposits along the Bruch membrane. RGR-d produced less severe disease with choriocapillaris and RPE atrophy, including focal accumulation of abnormal RGR-d protein at the basal boundary of the RPE. Degeneration of the choriocapillaris was marked by a decrease in endothelial CD31 protein and choriocapillaris breakdown at the ultrastructural level. Fundus lesions with patchy depigmentation were characteristic of old RGR-d mice. RGR-d was mislocalized in cultured cells and caused a strong cell growth defect. These results uphold the notion of a potential hidden link between AMD and a high-frequency RGR allele.

MeCP2-421-mediated RPE epithelial-mesenchymal transition and its relevance to the pathogenesis of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease. Epithelial-mesenchymal transition (EMT) of RPE cells plays an important role in the pathogenesis of PVR. In the current study, we sought to investigate the role of the methyl-CpG-binding protein 2 (MeCP2), especially P-MeCP2-421 in the pathogenesis of PVR. The expressions of P-MeCP2-421, P-MeCP2-80, PPAR-γ and the double labelling of P-MeCP2-421 with α-SMA, cytokeratin, TGF-ß and PPAR-γ in human PVR membranes were analysed by immunohistochemistry. The effect of knocking down MeCP2 using siRNA on the expressions of α-SMA, phospho-Smad2/3, collagen I, fibronectin and PPAR-γ; the expression of α-SMA stimulated by recombinant MeCP2 in ARPE-19; and the effect of TGF-ß and 5-AZA treatment on PPAR-γ expression were analysed by Western blot. Chromatin immunoprecipitation was used to determine the binding of MeCP2 to TGF-ß. Our results showed that P-MeCP2-421 was highly expressed in PVR membranes and was double labelled with α-SMA, cytokeratin and TGF-ß, knocking down MeCP2 inhibited the activation of Smad2/3 and the expression of collagen I and fibronectin induced by TGF-ß. TGF-ß inhibited the expression of PPAR-γ, silence of MeCP2 by siRNA or using MeCP2 inhibitor (5-AZA) increased the expression of PPAR-γ. α-SMA was up-regulated by the treatment of recombinant MeCP2. Importantly, we found that MeCP2 bound to TGF-ß as demonstrated by Chip assay. The results suggest that MeCP2 especially P-MeCP2-421 may play a significant role in the pathogenesis of PVR and targeting MeCP2 may be a potential therapeutic approach for the treatment of PVR.

Autophagy and autophagy-related proteins in cancer.

Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy.

The critical role of the interplays of EphrinB2/EphB4 and VEGF in the induction of angiogenesis.

The significant role of VEGF (vascular endothelial growth factor) as an angiogenesis inducer is well recognized. Besides VEGF, EphrinB2/EphB4 also plays essential roles in vascular development and postnatal angiogenesis. Compared with classical proangiogenic factors, not only does EphrinB2/EphB4 promote sprouting of new vessels, it is also involved in the vessel maturation. Given their involvement in many physiologic and pathological conditions, EphB4 and EphrinB2 are increasingly recognized as attractive therapeutic targets for angiogenesis-related diseases through modulating their expression and function. Previous works mainly focused on the individual role of VEGF and EphrinB2/EphB4 in angiogenesis, respectively, but the correlation between EphrinB2/EphB4 and VEGF in angiogenesis has not been fully disclosed. Here, we summarize the structure and bidirectional signaling of EphrinB2/EphB4, provide an overview on the relationship between EphrinB2/EphB4 signaling and VEGF pathway in angiogenesis and highlight the associated potential usefulness in anti-angiogenetic therapy.

Magnetization dynamics and its scattering mechanism in thin CoFeB films with interfacial anisotropy.

Studies of magnetization dynamics have incessantly facilitated the discovery of fundamentally novel physical phenomena, making steady headway in the development of magnetic and spintronics devices. The dynamics can be induced and detected electrically, offering new functionalities in advanced electronics at the nanoscale. However, its scattering mechanism is still disputed. Understanding the mechanism in thin films is especially important, because most spintronics devices are made from stacks of multilayers with nanometer thickness. The stacks are known to possess interfacial magnetic anisotropy, a central property for applications, whose influence on the dynamics remains unknown. Here, we investigate the impact of interfacial anisotropy by adopting CoFeB/MgO as a model system. Through systematic and complementary measurements of ferromagnetic resonance (FMR) on a series of thin films, we identify narrower FMR linewidths at higher temperatures. We explicitly rule out the temperature dependence of intrinsic damping as a possible cause, and it is also not expected from existing extrinsic scattering mechanisms for ferromagnets. We ascribe this observation to motional narrowing, an old concept so far neglected in the analyses of FMR spectra. The effect is confirmed to originate from interfacial anisotropy, impacting the practical technology of spin-based nanodevices up to room temperature.

APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective Trial. Report No. 2.

PURPOSE: We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy. METHODS: Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed. RESULTS: High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31-CTGF and cytokeratin-VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF. CONCLUSION: Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.

SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization.

SIRT1, a NAD(+) -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.

Review: Epigenetic mechanisms in ocular disease.

Epigenetics has become an increasingly important area of biomedical research. Increasing evidence shows that epigenetic alterations influence common pathologic responses including inflammation, ischemia, neoplasia, aging, and neurodegeneration. Importantly, epigenetic mechanisms may have a pathogenic role in many complex eye diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. The emerging emphasis on epigenetic mechanisms in studies of eye disease may provide new insights into the pathogenesis of complex eye diseases and aid in the development of novel treatments for these diseases.

[The advances of epigenetic research in eye].

Epigenetics is the emergence of a new branch of genetics. Epigenetic factors regulate gene function and phenotype by the modulation of DNA methylation, histone modification, non-coding RNA expression instead of changing the DNA sequence; more importantly, the regulation occurs under the influence of environment and diet and can be passed on to the next generation. Epigenetics is involved in life development, maintenance of normal physiological functions of the human body and the pathology of many complex phenomena,such as inflammation, aging, tumorgenesis, etc. There is no doubt that the pathogenesis of complex eye diseases such as recurrence of herpes simplex keratitis, glaucoma, uveitis and AMD may be associated with aberrant epigenetic regulations. Therefore effect in vigorously carrying eye research on epigenetics may provide new insight of the pathogenesis of those eye diseases and development of novel treatment options.

[Attach importance to eye epigenetic research].

Growing evidences show that the pathogenesis of majority human diseases is influenced by the abnormalities of epigenetic and genetic mechanism. The major epigenetic factors such as DNA methylation, histone modifications, and microRNA (miRNA) interact with each other to regulate gene expression and determine cell phenotype.Epigenetics is currently become a hot topic of biomedical research, which focus on how whole genome is regulated by epigenetics mechanism and its roles in life development, senescence, regeneration, tumorgenesis and the pathogenesis of complex disease. The occurrence of variety of eye diseases may be mediated through the interaction of environmental and genetic factors which in turn regulated by epigenetic mechanisms.Emphasizing the epigenetic research in eye may provide a new insight of the understanding of pathogenesis of complex eye disease and a novel approach of its treatment.

Distinct Role of Lycium barbarum L. Polysaccharides in Oxidative Stress-Related Ocular Diseases.

Oxidative stress is an imbalance between the increased production of reactive species and reduced antioxidant activity, which can cause a variety of disturbances including ocular diseases. Lycium barbarum polysaccharides (LBPs) are complex polysaccharides isolated from the fruit of L. barbarum, showing distinct roles in antioxidants. Moreover, it is relatively safe and non-toxic. In recent years, the antioxidant activities of LBPs have attracted remarkable attention. In order to illustrate its significance and underlying therapeutic value for vision, we comprehensively review the recent progress on the antioxidant mechanisms of LBP and its potential applications in ocular diseases, including diabetic retinopathy, hypertensive neuroretinopathy, age-related macular degeneration, retinitis pigmentosa, retinal ischemia/reperfusion injury, glaucoma, dry eye syndrome, and diabetic cataract.

The continuous treatment of anterior segment open globe injury: an eye injury vitrectomy study.

Background: The prognostic significance of debridement has long been demonstrated for trauma in tissues other than ocular. Unfortunately, the impact of wound healing in the anterior segment (AS) was not paid as much attention as in the posterior segment (PS). This study aims to evaluate whether a better prognosis can be obtained from continuous surgical treatment (CST) before fibrosis or scar formation in an open AS injury. Methods: In this prospective comparative cohort study, 19 eyes of 19 patients with an experience of AS open globe injury (OGI) were selected from the database of the eye injury vitrectomy study (EIVS) from January 1, 2020 to July 31, 2021. Of 19 patients, 9 who received CST were assigned to group 1, and 10 patients without CST after the initial wound repair were included in group 2. Comparison between the two groups was conducted in the final best corrected visual acuity (BCVA). Significant AS complications after injury were evaluated with χ2 test. The corneal leucoma area ratio, astigmatism, and the score of AS abnormalities were analyzed using the Student's t-test. Results: The differences of baseline clinical factors between the two groups were not statistically significant. The final BCVA was better in group 1 than in group 2 (P=0.011). The complications directly caused by AS injury, namely adhesive corneal leucoma, uneven anterior chamber, block of light passing through the pupil, and fibrosis or scarring, were more frequent in group 2 than in group 1 (P=0.011, 0.022, 0.037, and 0.040, respectively). Secondary glaucoma (3 cases) and severe AS structure destruction (2 cases) occurred only in group 2 (P=0.037 and 0.474, respectively). The area ratio of leucoma (0.79±0.44, 0.82±0.50, respectively) and corneal astigmatism (3.69±1.90, 4.50±4.80, respectively) revealed no statistical significance between the two groups. On the other hand, the score of AS abnormalities, mean values being 93.33±11.18 for group 1 and 67.00±29.46 for group 2, was statistically different (P=0.022). Conclusions: Initiating CST before fibrosis or scar formation might improve the prognosis of open AS injury, which was preferable to natural wound healing after wound repair.

Proteopathy Linked to Exon-Skipping Isoform of RGR-Opsin Contributes to the Pathogenesis of Age-Related Macular Degeneration.

Purpose: Proteopathy is believed to contribute to age-related macular degeneration (AMD). Much research indicates that AMD begins in the retinal pigment epithelium (RPE), which is associated with formation of extracellular drusen, a clinical hallmark of AMD. Human RPE produces a drusen-associated abnormal protein, the exon Ⅵ-skipping splice isoform of retinal G protein-coupled receptor (RGR-d). In this study, we investigate the detrimental effects of RGR-d on cultured cells and mouse retina. Methods: ARPE-19 cells were stably infected by lentivirus overexpressing RGR or RGR-d and were treated with MG132, sometimes combined with or without endoplasmic reticulum (ER) stress inducer, tunicamycin. RGR and RGR-d protein expression, degeneration pathway, and potential cytotoxicity were explored. Homozygous RGR-d mice aged 8 or 14 months were fed with a high-fat diet for 3 months and then subjected to ocular examination and histopathology experiments. Results: We confirm that RGR-d is proteotoxic under various conditions. In ARPE-19 cells, RGR-d is misfolded and almost completely degraded via the ubiquitin-proteasome system. Unlike normal RGR, RGR-d increases ER stress, triggers the unfolded protein response, and exerts potent cytotoxicity. Aged RGR-d mice manifest disrupted RPE cell integrity, apoptotic photoreceptors, choroidal deposition of complement C3, and CD86+CD32+ proinflammatory cell infiltration into retina and RPE-choroid. Furthermore, the AMD-like phenotype of RGR-d mice can be aggravated by a high-fat diet. Conclusions: Our study confirmed the pathogenicity of the RGR splice isoform and corroborated a significant role of proteopathy in AMD. These findings may contribute to greater comprehension of the multifactorial causes of AMD.

The essential role of N6-methyladenosine RNA methylation in complex eye diseases.

There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.

Over-expression of BMP4 inhibits experimental choroidal neovascularization by modulating VEGF and MMP-9.

Bone morphorgenetic protein (BMP)-4 has been shown to play a pivotal role in eye development; however, its role in mature retina or ocular angiogenic diseases is unclear. Activating downstream Smad signaling, BMP4 can be either pro-angiogenic or anti-angiogenic, depending on the context of cell types and associated microenvironment. In this study, we generated transgenic mice over-expressing BMP4 in retinal pigment epithelial (RPE) cells (Vmd2-Bmp4 Tg mice), and used the laser-induced choroidal neovascularization (CNV) model to study the angiogenic properties of BMP4 in adult eyes. Vmd2-Bmp4 Tg mice displayed normal retinal histology at 10 weeks of age when compared with age-matched wildtype mice. Over-expression of BMP4 in RPE in the transgenic mice was confirmed by real-time PCR and immunostaining. Elevated levels of Smad1,5 phosphorylation were found in BMP4 transgenic mice compared to wildype mice. Over-expression of BMP4 was associated with less severe CNV as characterized by fluorescein angiography, CNV volume measurement and histology. While control mice showed increased levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 after laser injury, Vmd2-Bmp4 Tg showed no increase in either VEGF or MMP-9. Further, we found that TNF-induced MMP-9 secretion in vitro was reduced by pretreatment of RPE cells with BMP4. The inhibition of MMP-9 was Smad-dependent because BMP4 failed to repress TNF-induced MMP-9 expression when Smad1,5 was silenced by siRNA. In summary, our studies identified an anti-angiogenic role for BMP4 in laser-induced CNV, mediated by direct inhibition of MMP-9 and indirect inhibition of VEGF.

alphaB-crystallin regulation of angiogenesis by modulation of VEGF.

alphaB-crystallin is a chaperone belonging to the small heat shock protein family. Herein we show attenuation of intraocular angiogenesis in alphaB-crystallin knockout (alphaB-crystallin(-/-)) mice in 2 models of intraocular disease: oxygen-induced retinopathy and laser-induced choroidal neovascularization. Vascular endothelial growth factor A (VEGF-A) mRNA and hypoxia inducible factor-1alpha protein expression were induced during retinal angiogenesis, but VEGF-A protein expression remained low in alphaB-crystallin(-/-) retina versus wild-type mice, whereas VEGF-R2 expression was not affected. Both alphaB-crystallin and its phosphorylated serine59 formwere expressed, and immunoprecipitation revealed alphaB-crystallin binding to VEGF-A but not transforming growth factor-beta in cultured retinal pigment epithelial (RPE) cells. alphaB-crystallin and VEGF-A are colocalized in the endoplasmic reticulum in RPE cells under chemical hypoxia. alphaB-crystallin(-/-) RPE showed low VEGF-A secretion under serum-starved conditions compared with wild-type cells. VEGF-A is polyubiquitinated in control and alphaB-crystallin siRNA treated RPE; however, mono-tetra ubiquitinated VEGF-A increases with alphaB-crystallin knockdown. Endothelial cell apoptosis in newly formed vessels was greater in alphaB-crystallin(-/-) than wild-type mice. Proteasomal inhibition in alphaB-crystallin(-/-) mice partially restores VEGF-A secretion and angiogenic phenotype in choroidal neovascularization. Our studies indicate an important role for alphaB-crystallin as a chaperone for VEGF-A in angiogenesis and its potential as a therapeutic target.

Transcriptional regulation of bone morphogenetic protein 4 by tumor necrosis factor and its relationship with age-related macular degeneration.

Bone morphogenetic protein-4 (BMP4) may be involved in the molecular switch that determines which late form of age-related macular degeneration (AMD) an individual develops. BMP4 expression is high in retinal pigment epithelium (RPE) cells in late, dry AMD patients, while BMP4 expression is low in the wet form of the disease, characterized by choroidal neovascularization (CNV). Here, we sought to determine the mechanism by which BMP4 is down-regulated in CNV. BMP4 expression was decreased within laser-induced CNV lesions in mice at a time when tumor necrosis factor (TNF) expression was high (7 d postlaser) and was reexpressed in RPE when TNF levels declined (14 d postlaser). We found that TNF, an important angiogenic stimulus, significantly down-regulates BMP4 expression in cultured human fetal RPE cells, ARPE-19 cells, and RPE cells in murine posterior eye cup explants. We identified two specificity protein 1 (Sp1) binding sites in the BMP4 promoter that are required for basal expression of BMP4 and its down-regulation by TNF. Through c-Jun NH(2)-terminal kinase (JNK) activation, TNF modulates Sp1 phosphorylation, thus decreasing its affinity to the BMP4 promoter. The down-regulation of BMP4 expression by TNF in CNV and mechanisms established might be useful for defining novel targets for AMD therapy.

Endoplasmic reticulum stress as a novel target to inhibit transdifferentiation of human retinal pigment epithelial cells.

BACKGROUND: The epithelial to mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a critical event in the pathogenesis of proliferative vitreoretinopathy and neovascular age-related macular degeneration, which are the leading causes of severe vision loss. Endoplasmic reticulum (ER) stress has been implicated in the EMT of many cell types and various ocular diseases. However, the relationship between ER stress and EMT in RPE cells remains unknown. Therefore, in the study, we explored the impact of ER stress on EMT in RPE cells. METHODS: Different concentrations of tunicamycin (TM) and thapsigargin (TG) were used to induce ER stress in human RPE cells. The expression of epithelial marker, mesenchymal markers and some of genes/proteins involved in TGF-ß/Smad signaling were analized by qPCR, western blot or immunostaining at the condition with or without stimulation of TGF-ß2 (10 ng/mL). Boyden chamber and scratch assay were used to evaluate the migration of RPE cells, while cell viability and apoptosis of RPE cells were measured by MTT and TUNEL assay, respectively. RESULTS: Treatment of RPE cells with TM and TG (24 h) reduced the expression of α -SMA and FN, and increased the expression of Occludin in a dose dependent manner at protein level, which was highly associated with the expression of GRP78. Treatment with TGF-ß2 significantly increased the expression of α-SMA and FN, and decreased the expression of Occludin both in protein and mRNA levels, which was significantly inhibited by a 4h pre-treatment with TM. In addition, the expression of TGF-ßRII and Smad2/3, and mRNAs of TGF-ßRII and Smad3 were also decreased by the TM treatment. TM-induced ER stress inhibited RPE cell migration, and high concentrations of TM and TG reduced cell viability and induced apoptosis of RPE cells. CONCLUSIONS: Chemical induction of ER stress inhibited EMT and migration in RPE cells, possibly by inactivation of TGF-ß signaling, suggesting that regulation of ER stress in RPE cells may be a new approach to prevent the development of intraocular fibrosis.

Essential Role of Multi-Omics Approaches in the Study of Retinal Vascular Diseases.

Retinal vascular disease is a highly prevalent vision-threatening ocular disease in the global population; however, its exact mechanism remains unclear. The expansion of omics technologies has revolutionized a new medical research methodology that combines multiple omics data derived from the same patients to generate multi-dimensional and multi-evidence-supported holistic inferences, providing unprecedented opportunities to elucidate the information flow of complex multi-factorial diseases. In this review, we summarize the applications of multi-omics technology to further elucidate the pathogenesis and complex molecular mechanisms underlying retinal vascular diseases. Moreover, we proposed multi-omics-based biomarker and therapeutic strategy discovery methodologies to optimize clinical and basic medicinal research approaches to retinal vascular diseases. Finally, the opportunities, current challenges, and future prospects of multi-omics analyses in retinal vascular disease studies are discussed in detail.

Potential Impact of N6-Methyladenosine RNA Methylation on Vision Function and the Pathological Processes of Ocular Diseases: New Discoveries and Future Perspectives.

N6-methyladenosine (m6A) methylation/modification plays a critical role in various biological processes through post-transcriptional ribonucleic acid (RNA) modification, which involves RNA processing, nuclear export, translation and decay. Functionally, m6A modification may be involved in ocular cell growth and differentiation, stem cell identity, development, haemostasis and innate versus adaptive immunity. Aberrations in m6A methylation may mediate numerous pathological conditions in the eye, including microorganism infection, inflammation, autoimmune disease, senescence, degeneration, epithelial-mesenchymal transition, fibrosis, angiogenesis, tumorigenesis and complex eye diseases. In this review, we have discussed the relevance of m6A modification to precision medicine, stem cell directional differentiation, biomarkers of eye diseases and m6A methylation activators and inhibitors. In addition, we summarised the challenges and future research directions in the field related to visual function and eye diseases.