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Harry A Quigley, Casey Keuthan, Mary Pease, Elizabeth Kimball; Astrocytes of the optic nerve head in pig and human eyes have no aquaporin channels. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2651.
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© ARVO (1962-2015); The Authors (2016-present)
It has been proposed that glaucoma’s optic nerve (ON) injury is related to glymphatic pathway fluid movement and thus would be dependent on astrocytic aquaporin (AQP) channels . We have reported that AQPs are absent in the astrocytic lamina of rodent optic nerve head (ONH) . This study quantified regional AQP channel expression in astrocytes of the porcine and human retina, ONH and myelinated ON (MON).
In pig and human post mortem eyes, we immunolabeled sections containing retina, ONH and MON against AQP1, 4, and 9, myelin basic protein, glial fibrillary acidic protein (GFAP) and α-dystroglycan (αDG). AQP label was quantified in each region  and quantitative gene expression data were analyzed in retina, ONH and MON tissues separately by qPCR in pig eyes. Human eyes were confirmed to have no retinal or ON disease histologically and by pre-mortem history.
Pig and human eyes had abundant AQP4 in Müller cells, retinal astrocytes, and MON astrocytes, but minimal expression in the ONH lamina cribrosa. AQP1, 9 were present in retina, but not in ONH. Immunolabeling of GFAP and αDG were present and had similar staining patterns in ONH and MON. Quantitative AQP4 labeling was at background level in ONH, but substantial in MON (ONH vs MON, p≤0.01). AQP4 mRNA expression was minimal in ONH, but significantly higher in MON (p=0.0001). GFAP mRNA expression was uniform in ONH and MON.
The absence of AQP4 channels in ONH astrocytes is evolutionarily conserved in all mammals studied. Aqp4 knockout mice have no beneficial or detrimental outcomes in experimental glaucoma. The regionally specific lack of AQP channels in ONH astrocytes is likely to be a protective mechanism against swelling in the narrow ONH region. The glymphatic pathway is unlikely to play a role at the site of damage in glaucoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
Human (A) and Pig (B) ONH showing lack of label for AQP4 (green) in lamina cribrosa between dotted lines.
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