New strategies for neuro protection in glaucoma

Yang, Xiaofeng; Yan, Junwei

doi:10.3389/fcell.2022.983195

Front. Cell Dev. Biol.

2022

DOI: 10.3389/fcell.2022.983195

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New strategies for neuro protection in glaucoma

Xiaofeng Yang

Junwei Yan²

Abstract: Glaucoma is a progressive, irreversible loss of retinal ganglion cells (RGCs) and axons that results in characteristic optic atrophy and corresponding progressive visual field defect. The exact mechanisms underlying glaucomatous neuron loss are not clear. The main risk factor for glaucoma onset and development is high intraocular pressure (IOP), however traditional IOP-lowering therapies are often not sufficient to prevent degeneration of RGCs and the vision loss may progress, indicating the need for complemen… Show more

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Cited by 4 publications

References 48 publications

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Modeling complex age-related eye disease

Becker,

L'Ecuyer,

Jones

et al. 2024

Progress in Retinal and Eye Research

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Modeling complex age-related eye disease

Becker,

L'Ecuyer,

Jones

et al. 2024

Progress in Retinal and Eye Research

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A Mini-Review on Gene Therapy in Glaucoma and Future Directions

Anton,

Geamănu,

Iancu

et al. 2024

IJMS

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Glaucoma is a group of optic neuropathies characterized by the degeneration of retinal ganglion cells and the loss of their axons in the optic nerve. The only approved therapies for the treatment of glaucoma are topical medications and surgical procedures aimed at lowering intraocular pressure. Gene therapy involves the insertion, removal, or modification of genetic material within cells to repair or compensate for the loss of a gene’s function. It describes a process or technology that enables the genetic modification of cells to produce a therapeutic effect. However, changing the genetic material alone does not extend the duration of overexpression of proteins that combat disease, nor does it facilitate the production of new proteins for this purpose. We reviewed the literature concerning the use of gene therapy in the treatment of glaucoma and explored the future directions that this innovation may offer. Three genes associated with glaucoma have been identified within these loci: myocilin/trabecular meshwork glucocorticoid response (TIGR) (GLC1A), optineurin (GLC1E), and WDR36 (GLC1G). Among these, the most extensively studied glaucoma gene is myocilin (a TM-inducible glucocorticoid response gene). Building on previous successes, researchers have begun to apply genetic therapeutic approaches to alleviate or reduce symptoms associated with ocular hypertension (OHT) and glaucoma-like optic neuropathy (GON). It is evident that several therapeutic strategies exist that modulate aqueous humor production and flow, thereby regulating intraocular pressure (IOP) and protecting retinal ganglion cells (RGCs) from apoptosis. With the emergence of gene therapy as a potentially viable approach to preserving vision, new methods for managing glaucoma may soon become available. Genomic therapy is a promising treatment option for glaucoma patients and has significant potential for widespread clinical application.

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The concept of gene therapy for glaucoma

Sulak,

Liu,

Smedowski

2024

Neural Regeneration Research

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Gene therapies, despite of being a relatively new therapeutic approach, have a potential to become an important alternative to current treatment strategies in glaucoma. Since glaucoma is not considered a single gene disease, the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells, especially, in intraocular-pressure-independent manner. The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tropism to retinal ganglion cells, resulting in long-term expression and low immunogenic profile. The gene therapy studies recruit inducible and genetic animal models of optic neuropathy, like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model. Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors (i.e., brain derived neurotrophic factor, and its receptor TrkB ), regulation of apoptosis and neurodegeneration (i.e., Bcl-xl , Xiap , FAS system, nicotinamide mononucleotide adenylyl transferase 2, Digit3 and Sarm1 ), immunomodulation (i.e., Crry , C3 complement), modulation of neuroinflammation (i.e., erythropoietin), reduction of excitotoxicity (i.e., CamKIIα ) and transcription regulation (i.e., Max , Nrf2 ). On the other hand, some of gene therapy studies focus on lowering intraocular pressure, by impacting genes involved in both, decreasing aqueous humor production (i.e., aquaporin 1), and increasing outflow facility (i.e., COX2 , prostaglandin F2α receptor, RhoA/RhoA kinase signaling pathway, MMP1 , Myocilin ). The goal of this review is to summarize the current state-of-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

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New strategies for neuro protection in glaucoma

Cited by 4 publications

References 48 publications

Modeling complex age-related eye disease

Modeling complex age-related eye disease

A Mini-Review on Gene Therapy in Glaucoma and Future Directions

The concept of gene therapy for glaucoma

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