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Characterization of the Most Resistant and Vulnerable Retinal Ganglion Cell Subtypes in a Chronic Model of Glaucoma in Rat
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DOI：10.1167/iovs.66.13.5.png)
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Abstract
En 中文
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% f 5.15% to 20.26% f 2.64% (dorsal-nasal) and from 33.07% f 4.09% to 22.65% f 2.65% (ventral-temporal), indicating higher vulnerability. In contrast, OPN4-positive RGCs increased from 3.27% f 1.34% to 6.99% f 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.
Keywords:
retinal ganglion cell
subtypes
differential susceptibility
glaucoma
ooDSGCs
ipRGCs
CART
Foxp2
Islet1/2
osteopontin
SPP1
melanopsin
OPN4
Tbr2
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