Browsing by Author "Chukwuka, C"

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    Genetic Insights and Epidemiological Models in Understanding Primary Open Angle Glaucoma
    (Ms. M. B. Mondal, 2024-11) Umezurike, BC; Akhimien, MO; Chukwuka, C; Ejike, TC; Ugwulor, L; Ajoku, B; Ijioma, SN.
    Primary open-angle glaucoma (POAG) is a multifactorial chronic optic neuropathy with significant genetic heterogeneity. The pathogenesis of POAG involves an imbalance between the production and drainage of aqueous humor (AH). Genetic theories suggest that transgenic mice demonstrating the GLU50LYS mutation in optineurin (OPTN) experience retinal ganglion cell apoptosis, while mutant myocilin (MYOC) proteins induce endoplasmic reticulum (ER) stress, leading to an unfolded protein response (UPR) and subsequent apoptosis of trabecular meshwork cells (TMC). Furthermore, the interaction between MYOC and mitochondria in the trabecular meshwork (TM) and astrocytes may lead to mitochondrial membrane depolarization and calcium channel dysregulation, contributing to POAG. Overexpression of MYOC variants (P370L, Q368X) is also implicated, as are epigenetic modifications and signaling pathways such as histone and DNA modification. POAG has been associated with autosomal dominant inheritance, with mutations in MYOC and OPTN being prominent causative factors, although many cases involve multiple genetic loci. Currently, over 20 genetic loci have been linked to POAG, with 14 chromosomal loci (GLC1A to GLC1N) identified, 5 of which contribute to juvenile-onset open-angle glaucoma (JOAG). Of these loci, MYOC, OPTN, WD repeat domain 36 (WDR36), and neurotrophin-4 (NTF4) are the most studied causative genes. The ongoing study of molecular genetics offers potential pathways for future therapeutic advances in the treatment of POAG.
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    The Genetics of Primary Open Angle Glaucoma Interventions: Therapeutic Directions and Future Predictions
    (Ms. M. B. Mondal, 2024-08) Umezurike, BC; Akhimien, MO; Chukwuka, C; Ejike, T; Ugwulor, L; Ajoku, B; Ijioma, SN.
    The “multifactorial chronic optic neuropathy” known as primary open angle glaucoma (POAG) is typified by a “progressive loss of retinal ganglion cells (RGC), structural damage to the retinal nerve fiber layer (RNFL) and optic nerve head (ONH), as well as abnormalities in the visual field.” High intraocular pressure (IOP), age, genetics, family history, race, etc. are the main risk factors. One of the pathological implications of POAG is “pressure-induced” ONH damage, which results in modifications to the expression of retinal genes. The ensuing fluid backup raises IOP, which damages optic nerve and results in POAG. Numerous susceptibility genes and environmental factors contribute to the “genetic heterogeneity” of POAG, according to genetic studies. “A set of twelve chromosomal loci, referred to as GLC1A through GLC1L, have been mapped for POAG. Three genes—myocilin (MYOC), optic neuropathy-inducing protein (Optineurin, OPTN)), and WD repeat domain 36 (WDR36)—have been identified as the GLC1A, GLC1E, and GLC1G”. A better understanding of the molecular genetic pathways and the pathological mechanisms involving the disease-causing genes, may help clarify the pathophysiology that leads to the disease and a targeted treatment. The role of genetics in POAG highlights the importance of genes in recent research advances, their future directions, applications, and therapy. The advent of modern genetic discoveries and future directions in vector engineering makes the cure for POAG possible. The paradigm shift in glaucoma treatment has moved from direct RGC and ONH therapy to targeting associated brain centers.