Noelia Ruzafa, Xandra Pereiro, Laura Prieto-López, Aritz Urcola, Arantxa Acera, Elena Vecino
{"title":"慢性青光眼大鼠视网膜神经节细胞最耐药和最易感亚型的特征。","authors":"Noelia Ruzafa, Xandra Pereiro, Laura Prieto-López, Aritz Urcola, Arantxa Acera, Elena Vecino","doi":"10.1167/iovs.66.13.5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ganglion cells (RGCs) transmit visual information to the brain and are selectively affected in glaucoma, a neurodegenerative disease caused by increased intraocular pressure (IOP) leading to vision loss. Not all RGC subtypes are equally vulnerable; thus, this study aimed to comprehensively analyze the differential loss of RGC subtypes using a rat model of chronic glaucoma.</p><p><strong>Methods: </strong>A chronic glaucoma model was established by cauterizing three episcleral veins in rat eyes. IOP was measured using an applanation tonometer, and after 40 days animals were euthanized. Whole-mount retinas were immunostained. RGCs were labeled with anti-RNA-binding protein with multiple splicing (RBPMS; marks 100% of RGCs) and co-labeled with subtype-specific antibodies: CART, melanopsin (OPN4), Foxp2, Islet1/2, SPP1, and Tbr2. RGC loss and subtype distribution were quantified as percentages of RBPMS-positive cells in different retinal regions.</p><p><strong>Results: </strong>In glaucomatous eyes, RGC survival decreased in the retinal periphery, with 65.44% in the dorsal-nasal and 76.03% in the ventral-temporal regions. CART-positive RGCs dropped from 32.9% ± 5.15% to 20.26% ± 2.64% (dorsal-nasal) and from 33.07% ± 4.09% to 22.65% ± 2.65% (ventral-temporal), indicating higher vulnerability. In contrast, OPN4-positive RGCs increased from 3.27% ± 1.34% to 6.99% ± 2.31% (dorsal-nasal), suggesting greater intrinsically photosensitive RGC (ipRGC) resilience. Percentages of SPP1-, Foxp2-, Islet1/2-, and Tbr2-positive RGCs remained unchanged, suggesting proportional loss to total RGC reduction.</p><p><strong>Conclusions: </strong>RGC subtypes showed differing susceptibilities to IOP, with OPN4-positive RGCs (ipRGCs) being more resistant and CART-positive RGCs (ON-OFF direction-selective ganglion cells [ooDSGCs]) highly vulnerable. This highlights the need to study ooDSGC degeneration and explore targeted neuroprotection. Future research should develop therapies to protect, regenerate, or replace ooDSGCs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 13","pages":"5"},"PeriodicalIF":4.7000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characterization of the Most Resistant and Vulnerable Retinal Ganglion Cell Subtypes in a Chronic Model of Glaucoma in Rat.\",\"authors\":\"Noelia Ruzafa, Xandra Pereiro, Laura Prieto-López, Aritz Urcola, Arantxa Acera, Elena Vecino\",\"doi\":\"10.1167/iovs.66.13.5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Retinal ganglion cells (RGCs) transmit visual information to the brain and are selectively affected in glaucoma, a neurodegenerative disease caused by increased intraocular pressure (IOP) leading to vision loss. Not all RGC subtypes are equally vulnerable; thus, this study aimed to comprehensively analyze the differential loss of RGC subtypes using a rat model of chronic glaucoma.</p><p><strong>Methods: </strong>A chronic glaucoma model was established by cauterizing three episcleral veins in rat eyes. IOP was measured using an applanation tonometer, and after 40 days animals were euthanized. Whole-mount retinas were immunostained. RGCs were labeled with anti-RNA-binding protein with multiple splicing (RBPMS; marks 100% of RGCs) and co-labeled with subtype-specific antibodies: CART, melanopsin (OPN4), Foxp2, Islet1/2, SPP1, and Tbr2. RGC loss and subtype distribution were quantified as percentages of RBPMS-positive cells in different retinal regions.</p><p><strong>Results: </strong>In glaucomatous eyes, RGC survival decreased in the retinal periphery, with 65.44% in the dorsal-nasal and 76.03% in the ventral-temporal regions. CART-positive RGCs dropped from 32.9% ± 5.15% to 20.26% ± 2.64% (dorsal-nasal) and from 33.07% ± 4.09% to 22.65% ± 2.65% (ventral-temporal), indicating higher vulnerability. In contrast, OPN4-positive RGCs increased from 3.27% ± 1.34% to 6.99% ± 2.31% (dorsal-nasal), suggesting greater intrinsically photosensitive RGC (ipRGC) resilience. Percentages of SPP1-, Foxp2-, Islet1/2-, and Tbr2-positive RGCs remained unchanged, suggesting proportional loss to total RGC reduction.</p><p><strong>Conclusions: </strong>RGC subtypes showed differing susceptibilities to IOP, with OPN4-positive RGCs (ipRGCs) being more resistant and CART-positive RGCs (ON-OFF direction-selective ganglion cells [ooDSGCs]) highly vulnerable. This highlights the need to study ooDSGC degeneration and explore targeted neuroprotection. 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Characterization of the Most Resistant and Vulnerable Retinal Ganglion Cell Subtypes in a Chronic Model of Glaucoma in Rat.
Purpose: Retinal ganglion cells (RGCs) transmit visual information to the brain and are selectively affected in glaucoma, a neurodegenerative disease caused by increased intraocular pressure (IOP) leading to vision loss. Not all RGC subtypes are equally vulnerable; thus, this study aimed to comprehensively analyze the differential loss of RGC subtypes using a rat model of chronic glaucoma.
Methods: A chronic glaucoma model was established by cauterizing three episcleral veins in rat eyes. IOP was measured using an applanation tonometer, and after 40 days animals were euthanized. Whole-mount retinas were immunostained. RGCs were labeled with anti-RNA-binding protein with multiple splicing (RBPMS; marks 100% of RGCs) and co-labeled with subtype-specific antibodies: CART, melanopsin (OPN4), Foxp2, Islet1/2, SPP1, and Tbr2. RGC loss and subtype distribution were quantified as percentages of RBPMS-positive cells in different retinal regions.
Results: In glaucomatous eyes, RGC survival decreased in the retinal periphery, with 65.44% in the dorsal-nasal and 76.03% in the ventral-temporal regions. CART-positive RGCs dropped from 32.9% ± 5.15% to 20.26% ± 2.64% (dorsal-nasal) and from 33.07% ± 4.09% to 22.65% ± 2.65% (ventral-temporal), indicating higher vulnerability. In contrast, OPN4-positive RGCs increased from 3.27% ± 1.34% to 6.99% ± 2.31% (dorsal-nasal), suggesting greater intrinsically photosensitive RGC (ipRGC) resilience. Percentages of SPP1-, Foxp2-, Islet1/2-, and Tbr2-positive RGCs remained unchanged, suggesting proportional loss to total RGC reduction.
Conclusions: RGC subtypes showed differing susceptibilities to IOP, with OPN4-positive RGCs (ipRGCs) being more resistant and CART-positive RGCs (ON-OFF direction-selective ganglion cells [ooDSGCs]) highly vulnerable. This highlights the need to study ooDSGC degeneration and explore targeted neuroprotection. Future research should develop therapies to protect, regenerate, or replace ooDSGCs.
期刊介绍：
Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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