Thrombospondin 1 Mediates Autophagy Upon Inhibition of the Rho-Associated Protein Kinase Inhibitor.

Age-related macular degeneration (AMD) is a degenerative eye disease leading to central vision loss and is characterized by dysregulated autophagy of the retinal pigment epithelium (RPE) layer. Recent studies have suggested that rho-associated protein kinase (ROCK) inhibitors may enhance autophagy in neurodegenerative diseases and promote the survival of RPE cells. This study investigated the effect of ROCK inhibitors on autophagy gene expression and autophagic vacuole formation in a human RPE (ARPE-19) cell line.

Combination effect of optical defocus and low dose atropine in myopia control: Study protocol for a randomized clinical trial.

Background: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.

Strategies to address inequity of uncorrected refractive error in the Western Pacific: A modified Delphi process.

Purpose: Uncorrected refractive error is the leading cause of vision impairment globally; however, little attention has been given to equity and access to services. This study aimed to identify and prioritise: (1) strategies to address inequity of access to refractive error services and (2) population groups to target with these strategies in five sub-regions within the Western Pacific.

Methods: We invited eye care professionals to complete a two-round online prioritisation process.

Coenzyme Q10 eyedrops conjugated with vitamin E TPGS alleviate neurodegeneration and mitochondrial dysfunction in the diabetic mouse retina.

Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy.

Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases.

Defocus incorporated multiple segments (DIMS) spectacle lenses increase the choroidal thickness: a two-year randomized clinical trial.

Background: Myopia control interventions, such as defocus incorporated multiple segments (DIMS) spectacle lenses, have been adopted in school-aged children to reduce the prevalence of myopia and its complications. This study aimed to investigate the effect of DIMS spectacle lenses on subfoveal choroidal thickness (SfChT) over a period of two years, as the choroidal response to myopic control is a crucial factor in exploring its potential effect on predicting myopia progression.

Methods: This study involved a secondary analysis of our previous randomized clinical trial.

Functional and structural changes in the neuroretina are accompanied by mitochondrial dysfunction in a type 2 diabetic mouse model.

Background: Diabetic retinopathy (DR), one of the leading causes of blindness and vision impairment, is suggested to exhibit functional and structural changes in retinal neurons as the earliest manifestation, which could be used to predict the progression of related angiopathy. While neural function and survival rely on proper mitochondrial function, and a growing body of literature has supported the role of mitochondrial dysfunction in the development of DR, how diabetes affects mitochondrial function in retinal tissue remains elusive. This study primarily aimed to investigate mitochondrial functional changes in a diabetic rodent model.

Retinal ganglion cells encode differently in the myopic mouse retina?

The etiology of myopia remains unclear. This study investigated whether retinal ganglion cells (RGCs) in the myopic retina encode visual information differently from the normal retina and to determine the role of Connexin (Cx) 36 in this process. Generalized linear models (GLMs), which can capture stimulus-dependent changes in real neurons with spike timing precision and reliability, were used to predict RGCs responses to focused and defocused images in the retinas of wild-type (normal) and Lens-Induced Myopia (LIM) mice.

TFEB is a central regulator of the aging process and age-related diseases.

Old age is associated with a greater burden of disease, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as other chronic diseases. Coincidentally, popular lifestyle interventions, such as caloric restriction, intermittent fasting, and regular exercise, in addition to pharmacological interventions intended to protect against age-related diseases, induce transcription factor EB (TFEB) and autophagy. In this review, we summarize emerging discoveries that point to TFEB activity affecting the hallmarks of aging, including inhibiting DNA damage and epigenetic modifications, inducing autophagy and cell clearance to promote proteostasis, regulating mitochondrial quality control, linking nutrient-sensing to energy metabolism, regulating pro- and anti-inflammatory pathways, inhibiting senescence and promoting cell regenerative capacity.

Long-term myopia control effect and safety in children wearing DIMS spectacle lenses for 6 years.

This study evaluated the long-term myopia control effect and safety in children wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses. Participants who completed the 2-year RCT were followed for a total of 6 years; their cycloplegic refractions and axial length were measured. Group 1 (n = 36) wore DIMS spectacles for 6 years; Group 2 (n = 14) wore DIMS lens for the first 3.

Additive effects of narrowband light and optical defocus on chick eye growth and refraction.

Background: In the past decade and during the COVID pandemic, the prevalence of myopia has reached epidemic proportions. To address this issue and reduce the prevalence of myopia and its complications, it is necessary to develop more effective interventions for controlling myopia. In this study, we investigated the combined effects of narrowband lights and competing defocus on eye growth and refraction in chicks, an important step in understanding the potential for these interventions to control myopia.

Changes in relative peripheral refraction in children who switched from single-vision lenses to Defocus Incorporated Multiple Segments lenses.

Purpose: To investigate changes in relative peripheral refraction (RPR) associated with myopia progression in children who wore single-vision (SV) lenses for 2 years and switched to Defocus Incorporated Multiple Segments (DIMS) lenses in the third year versus children who wore DIMS lenses for 3 years.

Methods: In the first 2 years, children were allocated randomly to wear either DIMS or SV lenses. In the third year, children in the DIMS group continued to wear these lenses, while those in the SV group were switched to DIMS lenses (Control-to-DIMS group).

Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia.

Diabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditions, photoreceptor cells have received relatively little attention with respect to the development of DR.

Postnatal eye size in mice is controlled by SREBP2-mediated transcriptional repression of Lrp2 and Bmp2.

Eye size is a key parameter of visual function, but the precise mechanisms of eye size control remain poorly understood. Here, we discovered that the lipogenic transcription factor sterol regulatory element-binding protein 2 (SREBP2) has an unanticipated function in the retinal pigment epithelium (RPE) to promote eye size in postnatal mice. SREBP2 transcriptionally represses low density lipoprotein receptor-related protein 2 (Lrp2), which has been shown to restrict eye overgrowth.

Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells.

In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ.

SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina.

Most of the previous myopic animal studies employed a single-candidate approach and lower resolution proteomics approaches that were difficult to detect minor changes, and generated limited systems-wide biological information. Hence, a complete picture of molecular events in the retina involving myopic development is lacking. Here, to investigate comprehensive retinal protein alternations and underlying molecular events in the early myopic stage, we performed a data-independent Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) based proteomic analysis coupled with different bioinformatics tools in pigmented guinea pigs after 4-day lens-induced myopia (LIM).

High-pH reversed-phase fractionated neural retina proteome of normal growing C57BL/6 mouse.

The retina is a key sensory tissue composed of multiple layers of cell populations that work coherently to process and decode visual information. Mass spectrometry-based proteomics approach has allowed high-throughput, untargeted protein identification, demonstrating the presence of these proteins in the retina and their involvement in biological signalling cascades. The comprehensive wild-type mouse retina proteome was prepared using a novel sample preparation approach, the suspension trapping (S-Trap) filter, and further fractionated with high-pH reversed phase chromatography involving a total of 28 injections.

Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.

All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention.

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells.

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes and , as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2.

Increased Connexin36 Phosphorylation in AII Amacrine Cell Coupling of the Mouse Myopic Retina.

Myopia is a substantial public health problem worldwide. In the myopic retina, distant images are focused in front of the photoreceptors. The cells and mechanisms for retinal signaling that account either for emmetropization (i.

Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models.

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD.

Author Correction: Characterization of Retinal Ganglion Cell and Optic Nerve Phenotypes Caused by Sustained Intracranial Pressure Elevation in Mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Defocus Incorporated Multiple Segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial.

Aim: To determine if 'Defocus Incorporated Multiple Segments' (DIMS) spectacle lenses slow childhood myopia progression.

Methods: A 2-year double-masked randomised controlled trial was carried out in 183 Chinese children aged 8-13 years, with myopia between -1.00 and -5.

Data on differentially expressed proteins in retinal emmetropization process in guinea pig using integrated SWATH-based and targeted-based proteomics.

Myopia is generally regarded as a failure of normal emmetropization process, however, its underlying molecular mechanisms are unclear. Retinal protein profile changes using integrated SWATH and MRM-HR MS were studied in guinea pigs at 3- and 21-days of age, where the axial elongation was significantly detected. Differential proteins expressions were identified, and related to pathways which are important in postnatal development in retina, proliferation, breakdown of glycogen-energy and visual phototransduction.