The role of lysophosphatidic acid and its receptors in corneal nerve regeneration DOI Creative Commons
Maryam Kheyrollah, Nicola Brandt, Anja U. Bräuer

et al.

The Ocular Surface, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

The integrity of corneal nerves is critical for ocular surface health, and damages can lead to Neurotrophic Keratopathy (NK). Despite the regenerative abilities peripheral nerve system (PNS), regeneration often incomplete, underlying mechanisms are poorly understood. This study aims identify potential factors that enhance NK treatment, with a focus on Lysophosphatidic acid (LPA). Thus, effect LPA its pathways in investigated detail using vitro mouse sensory neurons. To elucidate impact as well reveal responsible receptor, several functional assays siRNA-based knock-down experiments were conducted. Additionally, possible changes mRNA levels. LPA-treated neurons significantly reduced fiber growth. However, LPAR2 knockdown (Lpar2-KD) following treatment showed significant increase length. demonstrated enhanced levels Lpar2 mRNA. On other hand, indicators such Ngf, Gap-43, Cdc42, along downstream signaling components like Pi3k Ras, elevated Lpar2-KD In conclusion, this elucidates inhibitory effects outgrowth Furthermore, was identified receptor effect. might be promising therapeutic approach neuronal patients NK.

Language: Английский

Gene therapy strategies for glaucoma from IOP reduction to retinal neuroprotection: Progress towards non-viral systems DOI

Antoine M. Hakim,

Benjamin Guido,

Lokesh Narsineni

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 196, P. 114781 - 114781

Published: March 20, 2023

Language: Английский

Citations

32

Advances in Regenerative Medicine, Cell Therapy, and 3D Bioprinting for Glaucoma and Retinal Diseases DOI
Kevin Y. Wu, Rahma M Osman,

Obinna Esomchukwu

et al.

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1

Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies DOI Creative Commons

L. H. Wang,

Chun-Hao Huang,

I‐Chan Lin

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1261 - 1261

Published: Sept. 25, 2024

Glaucoma is a major global health concern and the leading cause of irreversible blindness worldwide, characterized by progressive degeneration retinal ganglion cells (RGCs) their axons. This review focuses on need for neuroprotective strategies in glaucoma management, addressing limitations current treatments that primarily target intraocular pressure (IOP) reduction. Despite effective IOP many patients continue to experience RGC degeneration, blindness. provides an overview both pharmacological interventions emerging technologies aimed at directly protecting RGCs optic nerve, independent Pharmacological agents such as brimonidine, neurotrophic factors, memantine, Ginkgo biloba extract, citicoline, nicotinamide, insulin, resveratrol show promise preclinical early clinical studies properties. Emerging technologies, including stem cell therapy, gene mitochondrial-targeted therapies, nanotechnologies, offer innovative approaches neuroprotection regeneration damaged RGCs. While these hold significant potential, further research trials are necessary confirm efficacy establish role practice. highlights multifaceted nature glaucoma, aiming guide future practice toward more management glaucoma-induced neurodegeneration.

Language: Английский

Citations

4

Molecular Findings Before Vision Loss in the Streptozotocin-Induced Rat Model of Diabetic Retinopathy DOI Creative Commons
Mădălina Anca Moldovan, Roxana-Denisa Capraş, Raluca Paşcalău

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(1), P. 28 - 28

Published: Jan. 4, 2025

The streptozotocin-induced rat model of diabetic retinopathy presents similarities to the disease observed in humans. After four weeks following induction diabetes, rats experience vision impairment. During this crucial four-week period, significant changes occur, with vascular damage standing out as a clinically factor, alongside neovascularization. While redox imbalance, activation microglia, secretion pro-inflammatory cytokines, and neuronal cell death are also observed, latter remains an emerging hypothesis requiring further exploration. This review is comprehensive up-to-date chronological depiction progression within initial hyperglycemia, which precede onset loss. data structured weekly changes. In first week, oxidative stress triggers retinal produces inflammation, leading altered neurotransmission. second week characterized by leukostasis, promotes ischemia, while neural degeneration begins accompanied simultaneous increase vessel permeability. inflammatory imbalances third week. Finally, fourth developments occur vessels dilate become tortuous, neovascularization develops, thickness diminishes, ultimately Through clearly outline, aims delineate framework for retinopathy.

Language: Английский

Citations

0

Sex-specific attenuation of photoreceptor degeneration by reserpine in a rhodopsin P23H rat model of autosomal dominant retinitis pigmentosa DOI Open Access
Hyun Beom Song, Laura Campello, Anupam K. Mondal

et al.

Published: Jan. 21, 2025

Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form IRD, is characterized by gradual dysfunction degeneration rod photoreceptors, followed loss cone photoreceptors. Recently, we identified reserpine as lead molecule for maintaining survival in mouse human organoids well rd16 mouse, which phenocopy Leber congenital amaurosis caused mutations cilia-centrosomal gene CEP290 (Chen et al. eLife 2023;12:e83205. DOI: https://doi.org/10.7554/eLife.83205). Here, show therapeutic potential rhodopsin P23H rat model autosomal dominant RP. At postnatal day (P) 68, when males females are analyzed together, reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to controls with little or no change a-wave cone-derived photopic b-wave. Interestingly, female display enhanced a- b-waves responses at P68, along better contrast threshold increased outer nuclear layer thickness. The demonstrate preservation both photoreceptors following treatment. Retinal transcriptome analysis reveals sex-specific reserpine, significant upregulation phototransduction genes proteostasis-related pathways, notably, associated stress response. This study builds upon our previously reported results reaffirming gene-agnostic treatment IRDs emphasizes importance biological sex disease research therapy development.

Language: Английский

Citations

0

Sex-specific attenuation of photoreceptor degeneration by reserpine in a rhodopsin P23H rat model of autosomal dominant retinitis pigmentosa DOI Open Access
Hyun Beom Song, Laura Campello, Anupam K. Mondal

et al.

Published: Jan. 21, 2025

Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form IRD, is characterized by gradual dysfunction degeneration rod photoreceptors, followed loss cone photoreceptors. Recently, we identified reserpine as lead molecule for maintaining survival in mouse human organoids well rd16 mouse, which phenocopy Leber congenital amaurosis caused mutations cilia-centrosomal gene CEP290 (Chen et al., 2023). Here, show therapeutic potential rhodopsin P23H rat model autosomal dominant RP. At postnatal day (P) 68, when males females are analyzed together, reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to controls with little or no change a-wave cone-derived photopic b-wave. Interestingly, female display enhanced a- b-waves responses at P68, along better contrast threshold increased outer nuclear layer thickness. The demonstrate preservation both photoreceptors following treatment. Retinal transcriptome analysis reveals sex-specific reserpine, significant upregulation phototransduction genes proteostasis-related pathways, notably, associated stress response. This study builds upon our previously reported results reaffirming gene-agnostic treatment IRDs emphasizes importance biological sex disease research therapy development.

Language: Английский

Citations

0

Looking to the Future of Viral Vectors in Ocular Gene Therapy: Clinical Review DOI Creative Commons

Chulpan B. Kharisova,

Kristina V. Kitaeva, Valeriya V. Solovyeva

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 365 - 365

Published: Feb. 5, 2025

Eye diseases can significantly affect the quality of life patients due to decreased visual acuity. Although modern ophthalmological diagnostic methods exist, some system are asymptomatic in early stages. Most seek advice from an ophthalmologist as a result rapidly progressive manifestation symptoms. A number inherited and acquired eye have only supportive treatment without eliminating etiologic factor. promising solution this problem may be gene therapy, which has proven efficacy safety shown clinical studies. By directly altering or replacing defective genes, therapeutic approach will stop well reverse progression diseases. This review examines concept therapy its application field ocular pathologies, emphasizing most recent scientific advances their potential impacts on function status.

Language: Английский

Citations

0

Sex-specific attenuation of photoreceptor degeneration by reserpine in a rhodopsin P23H rat model of autosomal dominant retinitis pigmentosa DOI Open Access
Hyun Beom Song, Laura Campello, Anupam K. Mondal

et al.

Published: March 27, 2025

Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form IRD, is characterized by gradual dysfunction degeneration rod photoreceptors, followed loss cone photoreceptors. Recently, we identified reserpine as lead molecule for maintaining survival in mouse human organoids well rd16 mouse, which phenocopy Leber congenital amaurosis caused mutations cilia-centrosomal gene CEP290 (Chen et al., 2023). Here, show therapeutic potential rhodopsin P23H rat model autosomal dominant RP. At postnatal day (P) 68, when males females are analyzed together, reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to controls with little or no change a-wave cone-derived photopic b-wave. Interestingly, female display enhanced a- b-waves responses at P68, along better contrast threshold increased outer nuclear layer thickness. The demonstrate preservation both photoreceptors following treatment. Retinal transcriptome analysis reveals sex-specific reserpine, significant upregulation phototransduction genes proteostasis-related pathways, notably, associated stress response. This study builds upon our previously reported results reaffirming gene-agnostic treatment IRDs emphasizes importance biological sex disease research therapy development.

Language: Английский

Citations

0

Sex-specific attenuation of photoreceptor degeneration by reserpine in a rhodopsin P23H rat model of autosomal dominant retinitis pigmentosa DOI Creative Commons
Hyun Beom Song, Laura Campello, Anupam K. Mondal

et al.

eLife, Journal Year: 2025, Volume and Issue: 14

Published: April 15, 2025

Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form IRD, is characterized by gradual dysfunction degeneration rod photoreceptors, followed loss cone photoreceptors. Recently, we identified reserpine as lead molecule for maintaining survival in mouse human organoids well rd16 mouse, which phenocopy Leber congenital amaurosis caused mutations cilia-centrosomal gene CEP290 (Chen et al., 2023). Here, show therapeutic potential rhodopsin P23H rat model autosomal dominant RP. At postnatal day (P) 68, when males females are analyzed together, reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to controls with little or no change a-wave cone-derived photopic b-wave. Interestingly, female display enhanced a- b-waves responses at P68, along better contrast threshold increased outer nuclear layer thickness. The demonstrate preservation both photoreceptors following treatment. Retinal transcriptome analysis reveals sex-specific reserpine, significant upregulation phototransduction genes proteostasis-related pathways, notably, associated stress response. This study builds upon our previously reported results reaffirming gene-agnostic treatment IRDs emphasizes importance biological sex disease research therapy development.

Language: Английский

Citations

0

Nanobinders for Synaptotagmin 1 enable the analysis of synaptic vesicle dynamics in rodent and human models DOI Creative Commons
Rashi Goel,

Kristina Jevdokimenko,

Ronja Rehm

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Synaptic neurotransmission is a critical hallmark of brain activity and one the first processes to be affected in neural diseases. Monitoring this process, particular synaptic vesicle recycling, living cells has been instrumental unraveling mechanisms responsible for neurotransmitter release. However, currently available reporters suffer from major limitations such large probe size or lack suitability human neurons, hampering understanding pathophysiology. Here we describe NbLumSyt1 toolkit, panel nanobody-based affinity probes targeting luminal domain protein Synaptotagmin 1 (Syt1). These new tools enable quantitative, non-invasive imaging functional interrogation transmission with unprecedented precision, versatility cost efficiency, technologies ranging fixed-and live-cell super-resolution electron microscopy mass spectrometry. Overall, nanobinders provide valuable platform physiology pathophysiology, benefiting fundamental neuroscience translational efforts study develop treatments brain-related disorders.

Language: Английский

Citations

0