Bioengineering, Journal Year: 2024, Volume and Issue: 12(1), P. 6 - 6
Published: Dec. 25, 2024
Glaucoma, a progressive and multifactorial optic neurodegenerative disease, still poses significant challenges in both diagnosis management remains perpetual enigma [...].
Language: Английский
TNOA Journal of Ophthalmic Science and Research, Journal Year: 2024, Volume and Issue: 62(3), P. 294 - 300
Published: July 1, 2024
Abstract Glaucoma remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing rate vision loss from glaucoma. Medical management first line in adult glaucoma, and evolution medical therapy for glaucoma has followed an exponential curve. This narrative review briefs rapid development new medications drug delivery systems recent years. Newer may be able extend duration medically controlled delaying or possibly eliminating need surgery some patients. Alternative methods a key factor improving outcomes with currently available medications.
Language: Английский
Citations
1
Vision Research, Journal Year: 2024, Volume and Issue: 226, P. 108519 - 108519
Published: Nov. 16, 2024
Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in management glaucoma. A spontaneous genetic model glaucoma has been identified cats extensively characterized as a viable translational model, with eye size anatomy similar to humans. In this study we sought establish initial proof concept gene delivery feline RGCs via intravitreal injection AAV2 normal cats. Pre-retinal, posterior vitreal AAV2/2-CMV-GFP, was performed overlying area centralis 5 adult Immunosuppressive oral prednisolone administered perioperatively gradually tapered over 6-10wks post-injection. Ophthalmic examination pre- The GFP reporter expression morphological effects viral transduction on retina were monitored vivo using confocal scanning laser ophthalmoscopy (cSLO) optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals 6-10wks. Full-field electroretinograms (ERG) visual evoked potentials (VEP) recorded baseline Retinas examined by histology immunolabeling RGC marker RBPMS Müller cell astrocyte SOX9, retina, optic nerve (ON), tract lateral geniculate nucleus (LGN). GFP+ axons visualized cSLO 1-2 weeks No changes observed OCT but 3/5 eyes exhibited mild inflammation histology. Retinal ON function preserved injected compared untreated eyes. predominantly RBPMS+ well SOX9+ cells. fluorescence throughout fiber central pathway. Peak (up ∼ 20 %) regions high expression, < 1 % expressed across whole retina. Our data provide that pre-retinal AAV2/2 may represent feasible platform highlight need further refinement improve efficiency control low-grade inflammation.
Language: Английский
Citations
1
Vision Research, Journal Year: 2024, Volume and Issue: 227, P. 108533 - 108533
Published: Dec. 6, 2024
Glaucoma comprises a heterogeneous set of eye conditions that cause progressive vision loss. has complex etiology, with different genetic and non-genetic risk factors differ across populations. Although difficult to diagnose in early stages, compromised cellular signaling, dysregulation genes, homeostatic imbalance are common precursors injury subsequent death retinal ganglion cells (RGCs). Lowering intraocular pressure (IOP) remains the primary approach for managing glaucoma but IOP alone does not explain all risks. Orthogonal approaches such as large-scale screening, combined studies animal models have been instrumental identifying genes molecular pathways involved pathogenesis. Cell type dependent vulnerability among RGCs can reveal basis specific visual deficits. A growing body knowledge availability modern tools perform targeted assessments health facilitate development effective timely interventions rescue. This review highlights recent findings on molecules, cell types context pathophysiology treatment.
Language: Английский
Citations
1
PNAS Nexus, Journal Year: 2024, Volume and Issue: 4(1)
Published: Dec. 10, 2024
Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several that inhibit aggregation approved or in clinical trials Alzheimer's disease. Here, we developed targeting the aggregation-prone β-propeller olfactomedin (OLF) domain myocilin, variants which comprise strongest genetic link glaucoma cause early onset vision loss for million individuals worldwide. Mutant myocilin aggregates intracellularly endoplasmic reticulum (ER). Subsequent ER stress causes cytotoxicity hastens dysregulation intraocular pressure, primary risk factor most forms glaucoma. Our antibody discovery campaign yielded two recombinant antibodies: anti-OLF1 recognizes linear epitope, while anti-OLF2 is selective natively folded OLF inhibits vitro. By binding OLF, these engage autophagy/lysosomal degradation promote pathogenic mutant myocilins. This work demonstrates potential therapeutic disrupt ER-localized by altering fate folding intermediates. approach could be translated as precision medicine myocilin-associated situ expression. More generally, study supports enhancing lysosomal proteostasis decline other diseases.
Language: Английский
Citations
1
Current Opinion in Ophthalmology, Journal Year: 2023, Volume and Issue: 35(2), P. 131 - 137
Published: Dec. 20, 2023
To provide the latest advances on future use of gene therapy for treatment glaucoma.
Language: Английский
Citations
3
Eye, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 8, 2024
The transformative potential of genetic engineering in ophthalmology is remarkable, promising new treatments for a wide range blinding eye diseases. an attractive target organ approaches, part due to its relatively immune-privileged status, accessibility, and the ease monitoring efficacy safety. Consequently, has been at forefront advances recent years. development Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), base editors, prime transposases have enabled efficient specific gene modification. Ocular therapy continues progress, with delivery systems using viral / non-viral vectors novel promoters enhancers. New strategies achieve neuroprotection neuroregeneration are evolving, including direct in-vivo cell reprogramming optogenetic approaches. In this review, we discuss ocular engineering, examine their current therapeutic roles, explore use future reduce growing burden vision loss blindness.
Language: Английский
Citations
0
Bioengineering, Journal Year: 2024, Volume and Issue: 12(1), P. 6 - 6
Published: Dec. 25, 2024
Glaucoma, a progressive and multifactorial optic neurodegenerative disease, still poses significant challenges in both diagnosis management remains perpetual enigma [...].
Language: Английский
Citations
0