Elevated Intraocular Pressure Facilitates T-Cell–Mediated Retinal Ganglion Cell Loss
- 1Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
- 2Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
- 3College of Osteopathic Medicine, Des Moines University, Des Moines, Iowa, United States
Abstract
Purpose: Our previous work indicated that adoptive transfer of CD3⁺ T cells from glaucomatous mice into healthy recipients results in progressive retinal ganglion cell (RGC) loss, providing evidence that adaptive immune responses contribute to glaucoma pathogenesis. This study tested whether elevated intraocular pressure (EIOP) promotes T-cell–mediated RGC degeneration using an adoptive transfer model of autoreactive T cells primed against RGC antigens.
Methods: Splenocytes from donor mice that express a green fluorescent protein (GFP)–specific T-cell receptor were transferred into recipient mice expressing GFP in a subset of RGCs. Experimental mice underwent mild IOP elevation; controls remained normotensive or received lipopolysaccharide (LPS). GFP⁺ RGC survival was assessed by fundoscopy and retinal flat mounts. Retinal expression of vascular cell adhesion molecule 1 (Vcam1) was analyzed by immunofluorescence and quantitative PCR.
Results: Fundoscopy 8 weeks posttransfer revealed minimal loss of GFP+ RGCs in naive mice (−4.46%), normotensive controls (−2.83%, P = 0.9899), and LPS-treated animals (−4.5%, P > 0.9999). In contrast, EIOP animals lost 18.43% of GFP⁺ RGCs (P = 0.0034) in the central retina. Similar findings were also observed in retinal flat mounts. EIOP retinas also exhibited increased Vcam1 expression associated with retinal capillaries compared with naive controls.
Conclusions: These findings indicate that mild EIOP promotes T-cell–mediated degeneration of RGCs, particularly in the central retina. LPS-mediated disruption of the blood–retina barrier alone did not induce RGC loss, indicating that IOP-dependent processes may be required to breach the immune-protective environment of the retina. The increase in Vcam1 expression in EIOP retinas may represent a mechanism facilitating T-cell–mediated retinal neurodegeneration.
Related
- Relationship Between Visual Field, Intraocular Pressure, and Retinal Nerve Fiber Layer in Patients with Open-Angle Glaucoma and Depression Level
- Blood Lipid Levels and Intraocular Pressure in a Japanese Population: the JPHC-NEXT Eye Study
- Effects of recurrent aflibercept and ranibizumab on intraocular pressure in diabetic retinopathy and age-related macular degeneration
- Intraocular pressure changes after posterior sub-Tenon injection of triamcinolone acetonide in a sample of Iraqi patients with noninfectious uveitis
- Detecting Intraocular Pressure Harmonic Frequencies in Glaucoma and the Sampling Targets Needed to Identify Them With Self-Tonometry
BibTeX
@article{mayberry2026elevated,
title = {{Elevated Intraocular Pressure Facilitates T-Cell–Mediated Retinal Ganglion Cell Loss}},
author = {Jordan E. Mayberry and Shuyu Xian and Sandra Roy and Markus H. Kuehn},
journal = {Investigative Ophthalmology \& Visual Science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.68},
url = {https://doi.org/10.1167/iovs.67.12.68},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Elevated Intraocular Pressure Facilitates T-Cell–Mediated Retinal Ganglion Cell Loss
AU - Jordan E. Mayberry
AU - Shuyu Xian
AU - Sandra Roy
AU - Markus H. Kuehn
PY - 2026
DA - 2026/10/27
JO - Investigative Ophthalmology & Visual Science
DO - 10.1167/iovs.67.12.68
UR - https://doi.org/10.1167/iovs.67.12.68
AB - Purpose: Our previous work indicated that adoptive transfer of CD3⁺ T cells from glaucomatous mice into healthy recipients results in progressive retinal ganglion cell (RGC) loss, providing evidence that adaptive immune responses contribute to glaucoma pathogenesis. This study tested whether elevated intraocular pressure (EIOP) promotes T-cell–mediated RGC degeneration using an adoptive transfer model of autoreactive T cells primed against RGC antigens. Methods: Splenocytes from donor mice that express a green fluorescent protein (GFP)–specific T-cell receptor were transferred into recipient mice expressing GFP in a subset of RGCs. Experimental mice underwent mild IOP elevation; controls remained normotensive or received lipopolysaccharide (LPS). GFP⁺ RGC survival was assessed by fundoscopy and retinal flat mounts. Retinal expression of vascular cell adhesion molecule 1 (Vcam1) was analyzed by immunofluorescence and quantitative PCR. Results: Fundoscopy 8 weeks posttransfer revealed minimal loss of GFP+ RGCs in naive mice (−4.46%), normotensive controls (−2.83%, P = 0.9899), and LPS-treated animals (−4.5%, P > 0.9999). In contrast, EIOP animals lost 18.43% of GFP⁺ RGCs (P = 0.0034) in the central retina. Similar findings were also observed in retinal flat mounts. EIOP retinas also exhibited increased Vcam1 expression associated with retinal capillaries compared with naive controls. Conclusions: These findings indicate that mild EIOP promotes T-cell–mediated degeneration of RGCs, particularly in the central retina. LPS-mediated disruption of the blood–retina barrier alone did not induce RGC loss, indicating that IOP-dependent processes may be required to breach the immune-protective environment of the retina. The increase in Vcam1 expression in EIOP retinas may represent a mechanism facilitating T-cell–mediated retinal neurodegeneration.
SN - 0146-0404
SN - 1552-5783
ER -