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Markus H Kuehn, Oliver W Gramlich, Neal D Heuss, Cheyanne R Godwin, Dale S Gregerson; T and B Lymphocyte Deficiency in RAG1 Mice Decreases Retinal Ganglion Cell Loss in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2849. doi: https://doi.org/.
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We recently demonstrated that adoptive transfer of lymphocytes from glaucomatous mice can induce retinal ganglion cell (RGC) damage in recipient animals. These findings suggest that an immune response develops in glaucoma that could potentially contribute to vision loss in the disease. Here we are evaluating if absence of an immune response slows the progression of glaucomatous damage.
Elevated IOP was induced in one eye of normal C57BL/6J (B6) or RAG1 knockout mice by vector mediated expression of myocY437H. IOP was monitored by rebound tonometry. After 8 and 16 weeks mice (n=20/group) were sacrificed, enucleated, and the density of Brn3a positive retinal ganglion cell was determined in both the treated and the untreated contralateral eyes. Data were compared to those of mice having received injections of ‘empty’ vector. The number of extravascular CD3+ cells in the glaucoma retinas was determined using FACS and confirmed using immunohistochemistry.
IOP significantly increased in treated eyes and remained elevated throughout the 16 week period (28.1 vs.13.0 mmHg). No differences in IOP response were observed between RAG and control mice. After 16 weeks, the average RGC density in B6 mice decreased from 3,332±68 to 2,576±284 RGC/mm2 (p=1.9x10-4) in treated eyes and to 2,951± 254 RGC/mm2 in the contralateral eye with normal IOP (p=5.4x10-4). In contrast, RGC density in treated RAG eyes only decreased to 2,951±411 RGC/mm2 (p=0.18) and to 3,182±260 RGC/mm2 (p=0.15) in the contralateral eye. RGC sparing in RAG1 was statistically significant in both the treated (p=0.006) and untreated (p=0.02) eyes when compared to those of control B6 animals. Flow cytometry indicated that the retina of eyes with elevated IOP contains significantly more CD3+ cells than that of healthy mice (46.0±16.1 vs 27.1±16.3, p=0.025, n=8/group).
We demonstrate that elevated IOP causes significant RGC loss in normal B6, but not in T- and B cell deficient mice. Furthermore, our data suggest that unilateral glaucoma can cause RGC loss in the contralateral eye but, again, only in normal mice. Taken together, these data indicate that immune processes significantly contribute to the pathology of experimental glaucoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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