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Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function. While studies of mice lacking essential autophagy genes have revealed a predisposition to retinal degeneration, the consequences of a moderate reduction in autophagy, similar to that which occurs during physiological aging, remain unclear. Here, we described a retinal phenotype consistent with accelerated aging in mice carrying a haploinsufficiency for , a pro-autophagic gene. These mice showed protein aggregation in the retina and RPE, metabolic underperformance, and premature vision loss. Moreover, mice were more prone to retinal degeneration after RPE stress. These findings indicate that autophagy provides crucial support to RPE-retinal metabolism and protects the retina against stress and physiological aging. 4-HNE: 4-hydroxynonenal; AMBRA1: autophagy and beclin 1 regulator 1, AMD: age-related macular degeneration;; GCL: ganglion cell layer; GFAP: glial fibrillary acidic protein; GLUL: glutamine synthetase/glutamate-ammonia ligase; HCL: hierarchical clustering; INL: inner nuclear layer; IPL: inner plexiform layer; LC/GC-MS: liquid chromatography/gas chromatography-mass spectrometry; MA: middle-aged; MTDR: MitoTracker Deep Red; MFI: mean fluorescence intensity; NL: NHCl and leupeptin; Nqo: NAD(P)H quinone dehydrogenase; ONL: outer nuclear layer; OPL: outer plexiform layer; OP: oscillatory potentials; OXPHOS: oxidative phosphorylation; PCR: polymerase chain reaction; PRKC/PKCα: protein kinase C; POS: photoreceptor outer segment; RGC: retinal ganglion cells; RPE: retinal pigment epithelium; SI: sodium iodate; TCA: tricarboxylic acid.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980615 | PMC |
http://dx.doi.org/10.1080/15548627.2022.2103307 | DOI Listing |
Front Cell Neurosci
December 2024
Laboratorio de Neurobiología Molecular y Celular de la Glía, Facultad de Medicina, Departamento de Bioquímica, UNAM, Mexico City, Mexico.
Müller cells are the most abundant glial cells in the mammalian retina. Their morphology and metabolism enable them to be in close contact and interact biochemically and physically with almost all retinal cell types, including neurons, pericytes, endothelial cells, and other glial cells, influencing their physiology by releasing bioactive molecules. Studies indicate that Müller glial cells are the primary source of angiogenic growth factor secretion in the neuroretina.
View Article and Find Full Text PDFClin Ophthalmol
December 2024
Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Objective: To report the results and feasibility of a pilot expansion of the Toronto Tele-Retinal Screening Program in an elderly long-term care home.
Methods: Long term care patients with Type II diabetes mellitus (DM) were screened between April 1, 2022, and July 1, 2022. Demographic and health data were collected through surveys.
BMJ Open Ophthalmol
December 2024
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Objective: Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual impairment and blindness in the elderly. As AMD is a multifactorial disease, it is critical to explore useful biomarkers and pathological pathways underlying it. The purpose of this study is to summarise current metabolic profiles and further identify potential metabolic biomarkers and therapeutic targets in AMD, which could facilitate clinical diagnosis and treatment.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, China. Electronic address:
Chaperone mediated autophagy (CMA) represents a specialized mechanism of lysosomal protein breakdown, playing a crucial role as a metabolic pathway that helps to regulate and sustain cellular and systemic physiological equilibrium. Within the CMA process, proteins that contain sequences similar to KFERQ are specifically identified by the heat shock cognate protein 70. These proteins are then chaperoned to the lysosomes for subsequent degradation, a process facilitated by the lysosome associated membrane protein 2A.
View Article and Find Full Text PDFClin Ophthalmol
December 2024
Department of Ophthalmology, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
Background: Anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management of various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO)-related macular edema (ME), and neovascular age-related macular degeneration (nAMD). However, there remains a need to systematically assess its effectiveness across these distinct conditions.
Methodology: A systematic review was conducted to identify studies evaluating the efficacy of anti-VEGF therapy in improving ocular outcomes in patients with DME, RVO-related ME, and nAMD.
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