The murine retinal pigment epithelium requires peroxisomal β-oxidation to maintain lysosomal function and prevent dedifferentiation
Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2301733120. doi: 10.1073/pnas.2301733120. Epub 2023 Oct 20. ABSTRACT Retinal pigment epithelium (RPE) cells have to phagocytose shed photoreceptor outer segments (POS) on a daily basis over the lifetime of an organism, but the mechanisms involved in the digestion and recycling of POS lipids are poorly understood. […]
Understanding the complex genetics and molecular mechanisms underlying glaucoma
Mol Aspects Med. 2023 Oct 17;94:101220. doi: 10.1016/j.mam.2023.101220. Online ahead of print. ABSTRACT Glaucoma is the leading cause of irreversible blindness worldwide. Currently the only effective treatment for glaucoma is to reduce the intraocular pressure, which can halt the progression of the disease. Highlighting the importance of identifying individuals at risk of developing glaucoma and […]
Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration
bioRxiv. 2023 Sep 29:2023.09.27.559733. doi: 10.1101/2023.09.27.559733. Preprint. ABSTRACT Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression […]
Volume electron microscopy reveals human retinal mitochondria that align with reflective bands in optical coherence tomography [Invited]
Biomed Opt Express. 2023 Sep 27;14(10):5512-5527. doi: 10.1364/BOE.501228. eCollection 2023 Oct 1. ABSTRACT Mitochondria are candidate reflectivity signal sources in optical coherence tomography (OCT) retinal imaging. Here, we use deep-learning-assisted volume electron microscopy of human retina and in vivo imaging to map mitochondria networks in the outer plexiform layer (OPL), where photoreceptors synapse with second-order […]
A rare, likely pathogenic variant causing Leber’s hereditary optic neuropathy in three-generation females of an African-American family
Am J Ophthalmol Case Rep. 2023 Oct 5;32:101936. doi: 10.1016/j.ajoc.2023.101936. eCollection 2023 Dec. ABSTRACT PURPOSE: We report a rare, likely pathogenic variant gene causing Leber’s hereditary optic neuropathy (LHON) in three-generation female members of an African-American family. OBSERVATIONS: The granddaughter and mother presented with a subacute, painless visual loss in both eyes at age 10 […]
Lysosomes in retinal health and disease
Trends Neurosci. 2023 Oct 16:S0166-2236(23)00224-2. doi: 10.1016/j.tins.2023.09.006. Online ahead of print. ABSTRACT Lysosomes play crucial roles in various cellular processes – including endocytosis, phagocytosis, and autophagy – which are vital for maintaining retinal health. Moreover, these organelles serve as environmental sensors and act as central hubs for multiple signaling pathways. Through communication with other cellular […]
Development of novel cytoprotective small compounds inhibiting mitochondria-dependent cell death
iScience. 2023 Sep 17;26(10):107916. doi: 10.1016/j.isci.2023.107916. eCollection 2023 Oct 20. ABSTRACT We identified cytoprotective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in ocular disease mouse models. M109S directly interacted with […]
An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation
iScience. 2023 Sep 15;26(10):107921. doi: 10.1016/j.isci.2023.107921. eCollection 2023 Oct 20. ABSTRACT Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and […]
COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury
Exp Eye Res. 2023 Oct 13:109678. doi: 10.1016/j.exer.2023.109678. Online ahead of print. ABSTRACT Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory responses playing an important role in this process. COG1410, a mimetic peptide of apolipoprotein E, has demonstrated protective potential in the […]
Unveiling Neuroprotection and Regeneration Mechanisms in Optic Nerve Injury: Insight from Neural Progenitor Cell Therapy with Focus on Vps35 and Syntaxin12
Cells. 2023 Oct 6;12(19):2412. doi: 10.3390/cells12192412. ABSTRACT Axonal degeneration resulting from optic nerve damage can lead to the progressive death of retinal ganglion cells (RGCs), culminating in irreversible vision loss. We contrasted two methods for inducing optic nerve damage: optic nerve compression (ONCo) and optic nerve crush (ONCr). These were assessed for their respective merits […]