Retinal Diseases Research Articles

Age-related dysregulation of the retinal transcriptome in African turquoise killifish.

Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.

Unveiling the retinal secrets of neuromyelitis optica spectrum disorder

BackgroundVascular alterations are now recognized as important contributors to the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD). This study aimed to use optical coherence tomography (OCT) and OCT-angiography (OCTA) to assess alterations in the retinal structure and microvasculature in patients with NMOSD, so we can understand pathophysiology of NMOSD, implicating this on disease activity, visual outcome and management on the future.MethodsA case–control study was conducted on 40 NMOSD patients with (NMOSD + ON) and without (NMOSD – ON) history of optic neuritis and 36 healthy subjects. The following data were assessed in NMOSD patients: clinical history, EDSS, and visual function testing. Both groups underwent spectral domain (SD)-OCT and OCTA.ResultsIn this study, NMOSD + ON patients had a statistically significant reduction in all SD-OCT parameters compared to healthy control. Regarding OCTA, there was a significant reduction in radial peripapillary capillary density (RPCD) in NMOSD + ON (P-value < 0.001) and some sectors of NMOSD–ON compared to healthy control. NMOSD + ON patients had significant differences in RPCD compared to those without (P-value < 0.001).ConclusionsHere we show that the advance of this study is that retinal microvascular alterations have been noticed in NMOSD–ON eyes, indicating that subclinical primary retinal vasculopathy and disease activity may occur in NMOSD before onset of ON and retinal atrophy. This may have implications on early detection of disease activity, early interference in management and prognostic tool to visual outcome in following the patients.

Dark continuous noise from mutant G90D-rhodopsin predominantly underlies congenital stationary night blindness

Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One well-studied rhodopsin point mutant, G90D-Rho, is thought to cause CSNB because of its constitutive activity in darkness causing rod desensitization. However, the nature of this constitutive activity and its precise molecular source have not been resolved for almost 30 y. In this study, we made a knock-in (KI) mouse line with a very low expression of G90D-Rho (equal in amount to ~0.1% of normal rhodopsin, WT-Rho, in WT rods), with the remaining WT-Rho replaced by REY-Rho, a mutant with a very low efficiency of activating transducin due to a charge reversal of the highly conserved ERY motif to REY. We observed two kinds of constitutive noise: one being spontaneous isomerization (R*) of G90D-Rho at a molecular rate (R* s-1) 175-fold higher than WT-Rho and the other being G90D-Rho-generated dark continuous noise comprising low-amplitude unitary events occurring at a very high molecular rate equivalent in effect to ~40,000-fold of R* s-1 from WT-Rho. Neither noise type originated from G90D-Opsin because exogenous 11-cis-retinal had no effect. Extrapolating the above observations at low (0.1%) expression of G90D-Rho to normal disease exhibited by a KI mouse model with RhoG90D/WTand RhoG90D/G90D genotypes predicts the disease condition very well quantitatively. Overall, the continuous noise from G90D-Rho therefore predominates, constituting the major equivalent background light causing rod desensitization in CSNB.

Information Transmission through Biotic-Abiotic Interfaces to Restore or Enhance Human Function.

Advancements in reliable information transfer across biotic-abiotic interfaces have enabled the restoration of lost human function. For example, communication between neuronal cells and electrical devices restores the ability to walk to a tetraplegic patient and vision to patients blinded by retinal disease. These impactful medical achievements are aided by tailored biotic-abiotic interfaces that maximize information transfer fidelity by considering the physical properties of the underlying biological and synthetic components. This Review develops a modular framework to define and describe the engineering of biotic and abiotic components as well as the design of interfaces to facilitate biotic-abiotic information transfer using light or electricity. Delineating the properties of the biotic, interface, and abiotic components that enable communication can serve as a guide for future research in this highly interdisciplinary field. Application of synthetic biology to engineer light-sensitive proteins has facilitated the control of neural signaling and the restoration of rudimentary vision after retinal blindness. Electrophysiological methodologies that use brain-computer interfaces and stimulating implants to bypass spinal column injuries have led to the rehabilitation of limb movement and walking ability. Cellular interfacing methodologies and on-chip learning capability have been made possible by organic transistors that mimic the information processing capacity of neurons. The collaboration of molecular biologists, material scientists, and electrical engineers in the emerging field of biotic-abiotic interfacing will lead to the development of prosthetics capable of responding to thought and experiencing touch sensation via direct integration into the human nervous system. Further interdisciplinary research will improve electrical and optical interfacing technologies for the restoration of vision, offering greater visual acuity and potentially color vision in the near future.

The role of syntaxins in retinal function and health

The soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) superfamily plays a pivotal role in cellular trafficking by facilitating membrane fusion events. These SNARE proteins, including syntaxins, assemble into complexes that actively facilitate specific membrane fusion events. Syntaxins, as integral components of the SNARE complex, play a crucial role in initiating and regulating these fusion activities. While specific syntaxins have been extensively studied in various cellular processes, including neurotransmitter release, autophagy and endoplasmic reticulum (ER)-to-Golgi protein transport, their roles in the retina remain less explored. This review aims to enhance our understanding of syntaxins’ functions in the retina by shedding light on how syntaxins mediate membrane fusion events unique to the retina. Additionally, we seek to establish a connection between syntaxin mutations and retinal diseases. By exploring the intricate interplay of syntaxins in retinal function and health, we aim to contribute to the broader comprehension of cellular trafficking in the context of retinal physiology and pathology.

Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.

Central Retinal Vein Occlusion as the Debut of a Chronic Myeloproliferative Neoplasm

Introduction. Most retinal vascular diseases are associated with systemic risk factors such as hypertension, diabetes mellitus, age and smoking. However, in their absence, further examination is required to identify possible hematological disorders.Purpose. Improve the diagnostic and management scheme for patients with occlusion of the central retinal vein or its branches.Materials and methods. A clinical case of the onset of polycythemia vera with the central retinal vein occlusion is described. As part of the study, a molecular genetic analysis was carried out to identify the driver mutation JAK2V617F in peripheral blood as a screening diagnosis of Ph-negative chronic myeloproliferative neoplasms (CMN), a cytological, cytogenetic study of bone marrow aspirate and a morphological study of bone marrow trephine biopsy.Results. A mutant allele of the JAK2V617F gene with a diagnostically significant allele load of 14.61 % was determined in a patient hospitalized in the ophthalmology department with a diagnosis of central retinal vein occlusion (CRVO) of the right eye. The patient was referred for further examination to the Moscow City Hematology Center of Botkin City Clinical Hospital, where, aſter examination, the diagnosis was established: True polycythemia.Discussion. CMN are a group of tumor diseases of hematopoietic tissue characterized by malignant transformation of bone marrow stem cells with their subsequent clonal proliferation. Cytogenetic and molecular genetic disorders play a significant role in the pathogenesis of chronic CMN. True polycythemia, essential thrombocytemia, primary myelofibrosis belong to the group of classical Ph-negative CMP, Thrombotic, vascular and hemorrhagic complications are the most common causes of death in patients with this pathology.Conclusion. Previously, various ophthalmological manifestations and symptoms have been described in patients with CMN. The observed complications are diverse and oſten secondary to the pathognomonic hematological disorders for these diseases. It is worth considering the clinical value of molecular genetic analysis to detect the JAK2V617F mutation in patients with central retinal vein occlusion for early diagnosis of CMN and timely administration of appropriate therapy.

Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model.

Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP's structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.

Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model

Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are &gt;100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP’s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.

Multi-risk factors joint prediction model for risk prediction of retinopathy of prematurity

Abstract Purpose Retinopathy of prematurity (ROP) is a retinal vascular proliferative disease common in low birth weight and premature infants and is one of the main causes of blindness in children. In the context of predictive, preventive and personalized medicine (PPPM/3PM), early screening, identification and treatment of ROP will directly contribute to improve patients’ long-term visual prognosis and reduce the risk of blindness. Thus, our objective is to establish an artificial intelligence (AI) algorithm combined with clinical demographics to create a risk model for ROP including treatment-requiring retinopathy of prematurity (TR-ROP) infants. Methods A total of 22,569 infants who underwent routine ROP screening in Shenzhen Eye Hospital from March 2003 to September 2023 were collected, including 3335 infants with ROP and 1234 infants with TR-ROP among ROP infants. Two machine learning methods of logistic regression and decision tree and a deep learning method of multi-layer perceptron were trained by using the relevant combination of risk factors such as birth weight (BW), gestational age (GA), gender, whether multiple births (MB) and mode of delivery (MD) to achieve the risk prediction of ROP and TR-ROP. We used five evaluation metrics to evaluate the performance of the risk prediction model. The area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) were the main measurement metrics. Results In the risk prediction for ROP, the BW + GA demonstrated the optimal performance (mean ± SD, AUCPR: 0.4849 ± 0.0175, AUC: 0.8124 ± 0.0033). In the risk prediction of TR-ROP, reasonable performance can be achieved by using GA + BW + Gender + MD + MB (AUCPR: 0.2713 ± 0.0214, AUC: 0.8328 ± 0.0088). Conclusions Combining risk factors with AI in screening programs for ROP could achieve risk prediction of ROP and TR-ROP, detect TR-ROP earlier and reduce the number of ROP examinations and unnecessary physiological stress in low-risk infants. Therefore, combining ROP-related biometric information with AI is a cost-effective strategy for predictive diagnostic, targeted prevention, and personalization of medical services in early screening and treatment of ROP.

Diagnostic yield of an inherited retinal disease gene panel in retinopathy of unknown origin

Purpose: Evaluating the presence of class 3, 4 and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO). Methods: Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmological history, complete ophthalmological examination, anti-retinal antibodies and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: non-paraneoplastic autoimmune retinopathy (npAIR), unilateral pigmentary retinopathy (UPR), asymmetrical pigmentary retinopathy (APR) and acute zonal occult outer retinopathy (AZOOR). Results: We included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20 – 68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, 2 also demonstrated class 5 variants in other IRD genes. The remaining 5 patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) npAIR patient in our RUO cohort. When considering the npAIR subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved. Conclusions: Every suspected npAIR patient should benefit from gene panel testing in order not to overlook undiagnosed IRDs. In contrast, UPR, APR and AZOOR subpopulations did not benefit from genetic analysis in this study.

Inhibiting the SARM1-NAD+ axis reduces oxidative stress-induced damage to retinal and nerve cells

Retinal neurodegenerative diseases are a category of refractory blinding eye conditions closely associated with oxidative stress induced by mitochondrial dysfunction in retinal cells. SARM1, a core driver molecule leading to axonal degeneration, possesses NAD+ enzyme (NADase) activity. However, the role of the SARM1-NAD+ axis in oxidative stress-induced retinal cell death remains unclear. Here, we employed the SARM1 NADase inhibitor DSRM-3716 and established a glucose oxidase (GOx)-induced oxidative stress cell model. We found that compared to the GOx group, the DSRM-3716 pre-treated group reduced the hydrolysis of NAD+, inhibited the elevation of oxidative stress markers induced by GOx, decreased mitochondrial dysfunction, lowered the phosphorylation level of JNK, and attenuated the occurrence of pyroptosis in retinal and nerve cells, thereby providing protection for neurite growth. Further utilization of the JNK activator Anisomycin activated JNK, revealed that the JNK/c-Jun pathway down-regulated NMNAT2 expression. Consequently, it reduced cellular NAD+ synthesis, exacerbated mitochondrial dysfunction and cell pyroptosis, and reversed the protective effect of DSRM-3716 on cells. In summary, the inhibition of SARM1 NADase activity substantially mitigates oxidative damage to retinal cells and mitochondrial damage. Additionally, JNK simultaneously serves as both an upstream and downstream regulator in the SARM1-NAD+ axis, regulating retinal cell pyroptosis and neurite injury. Thus, this study provides new insights into the pathological processes of retinal cell oxidative stress and identifies potential therapeutic targets for retinal neurodegenerative diseases.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Prominin 1 is crucial for the early development of photoreceptor outer segments

Prominin 1 (PROM1) is a pentaspan transmembrane glycoprotein localized on the nascent photoreceptor discs. Mutations in PROM1 are linked to various retinal diseases. In this study, we assessed the role of PROM1 in photoreceptor biology and physiology using the PROM1 knockout murine model (rd19). Our study found that PROM1 is essential for vision and photoreceptor development. We found an early reduction in photoreceptor response beginning at post-natal day 12 (P12) before eye opening in the absence of PROM1 with no apparent loss in photoreceptor cells. However, at this stage, we observed an increased glial cell activation, indicative of cell damage. Contrary to our expectations, dark rearing did not mitigate photoreceptor degeneration or vision loss in PROM1 knockout mice. In addition to physiological defects seen in PROM1 knockout mice, ultrastructural analysis revealed malformed outer segments characterized by whorl-like continuous membranes instead of stacked disks. In parallel to the reduced rod response at P12, proteomics revealed a significant reduction in the levels of protocadherin, a known interactor of PROM1, and rod photoreceptor outer segment proteins, including rhodopsin. Overall, our results underscore the indispensable role of PROM1 in photoreceptor development and maintenance of healthy vision.

Small extracellular vesicles of organoid-derived human retinal stem cells remodel Müller cell fate via miRNA: A novel remedy for retinal degeneration

Remodeling retinal Müller glial fate, including gliosis inhibition and pro-reprogramming, represents a crucial avenue for treating degenerative retinal diseases. Stem cell transplantation exerts effects on modulating retinal Müller glial fate. However, the optimized stem cell products and the underlying therapeutic mechanisms need to be investigated. In the present study, we found that retinal progenitor cells from human embryonic stem cell-derived retinal organoids (hERO-RPCs) transferred extracellular vehicles (EVs) into Müller cells following subretinal transplantation into RCS rats. Small EVs from hERO-RPCs (hERO-RPC-sEVs) were collected and were found to delay photoreceptor degeneration and protect retinal function in RCS rats. hERO-RPC-sEVs were taken up by Müller cells both in vivo and in vitro, and inhibited gliosis while promoting early dedifferentiation of Müller cells. We further explored the miRNA profiles of hERO-RPC-sEVs, which suggested a functional signature associated with neuroprotection and development, as well as the regulation of stem cell and glial fate. Mechanistically, hERO-RPC-sEVs might regulate the fate of Müller cells by miRNA-mediated nuclear factor I transcription factors B (NFIB) downregulation. Collectively, our findings offer novel mechanistic insights into stem cell therapy and promote the development of EV-centered therapeutic strategies.

Quantitative investigation on the effects of eyeball geometry, blood perfusion and natural convection in retinal laser surgery

The photothermal effects of laser on tissue are widely used in ophthalmology to treat retinal diseases. The accurate modelling of retinal laser surgery will prove valuable guidance for clinic treatment. There are several important issues should be carefully evaluated during retinal laser surgery modelling, including the eye geometry (whole eye or fundus only, retinal pigment epithelium layer incorporated or not), blood perfusion and natural convection. In previous publications, the existence of the anterior part of eyeball and retinal pigment epithelium layer is neglected to simply the eye geometry due to low laser light absorption (anterior part of eyeball) or small volume occupation (retinal pigment epithelium layer), respectively. However, the justification of this treatment has not been conducted. In this study, we will quantitatively investigate these factors systemically in a large pulse duration range that covers all the retinal laser surgery used in clinic. To do this, we present a bioheat transfer model for the simulation of the thermal response of the eye to laser irradiation. In the simulation, the 3D whole-eye geometry is considered. The Pennes bioheat transfer equation is adopted for the whole-eye temperature modelling. Simultaneously, we treat the fundus as a multilayered medium that all primary components, including RPE layer, are considered for first time in whole eye modelling. Our model calculates the thermal responses of the eye during laser retinal surgery with the pulse duration from nanosecond to tens of second. The effects of eye geometry, blood perfusion and natural convection are clearly clarified based on the laser pulse duration and incident energy used. The results show that neglecting the anterior part of eyeball will introduce the computational error more than 27 %. The existence of the retinal pigment epithelium layer should always be considered in retinal laser surgery modelling in all pulse durations used in clinic, otherwise more than 20 % computational error will be generated. When the pulse duration is longer than 10s, the effect of blood perfusion and natural convection in vitreous body should both be considered.

Retinal ischemic diseases and promising therapeutic molecular targets.

Retinal ischemia is a fundamental pathologic condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, age-related macular degeneration, and other eye diseases. Extensive inflammation, redox imbalance, apoptosis, and abnormal vascular formation in retinal ischemia could lead to visual impairments. Developing or finding effective treatments is urgently needed to protect the eye against retinal ischemia and related damage. To address the demand, we have searched for promising therapeutic molecular targets in the eye (e.g., hypoxia-inducible factor [HIF], peroxisome proliferator-activated receptor-alpha [PPARα], and nicotinamide adenine dinucleotide [NAD+]), and found that modulations of each molecular target might protect the eye against retinal ischemic damage in terms of complex pathologic mechanisms. In the current article, we review and update the therapeutic evidence of modulation of HIF, PPARα, or NAD+ and discuss future directions for developing promising drugs based on these molecular targets. This summary urges research to obtain more solid evidence of each molecular target in retinal ischemic diseases.

Ensemble learning for retinal disease recognition under limited resources.

Retinal optical coherence tomography (OCT) images provide crucial insights into the health of the posterior ocular segment. Therefore, the advancement of automated image analysis methods is imperative to equip clinicians and researchers with quantitative data, thereby facilitating informed decision-making. The application of deep learning (DL)-based approaches has gained extensive traction for executing these analysis tasks, demonstrating remarkable performance compared to labor-intensive manual analyses. However, the acquisition of retinal OCT images often presents challenges stemming from privacy concerns and the resource-intensive labeling procedures, which contradicts the prevailing notion that DL models necessitate substantial data volumes for achieving superior performance. Moreover, limitations in available computational resources constrain the progress of high-performance medical artificial intelligence, particularly in less developed regions and countries. This paper introduces a novel ensemble learning mechanism designed for recognizing retinal diseases under limited resources (e.g., data, computation). The mechanism leverages insights from multiple pre-trained models, facilitating the transfer and adaptation of their knowledge to retinal OCT images. This approach establishes a robust model even when confronted with limited labeled data, eliminating the need for an extensive array of parameters, as required in learning from scratch. Comprehensive experimentation on real-world datasets demonstrates that the ensemble models constructed by the proposed ensemble method show superior performance over the baseline models under sparse labeled data, especially the triple ensemble model, which achieves the accuracy of 92.06%, which is 8.27%, 7.99%, and 11.14% better than the three baseline models, respectively. In addition, compared with the three baseline models learned from scratch, the triple ensemble model has fewer trainable parameters, only 3.677M, which is lower than the three baseline models of 8.013M, 4.302M, and 20.158M, respectively.

Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium

Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear.Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel RPE reporter mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.

Cross-Modal Attention Network for Retinal Disease Classification based on Multi-modal Images

Cross-Modal Attention Network for Retinal Disease Classification based on Multi-modal Images