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Simon Thompson, Grant Cull, Brad Fortune, Lin Wang; TrpV4 and GFAP expression within the optic nerve (ON) during non-human primate (NHP) experimental glaucoma (EG). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4950.
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© ARVO (1962-2015); The Authors (2016-present)
We hypothesized that one of the cellular components underlying hemodynamic changes in EG within the NHP ON are astrocytes, whose processes encasing the blood vessels are known to modify vascular activities. Since, TrpV4, a protein localized to astrocyte end-feet, as well as other cell types, has been shown to contribute to vascular activities; we quantified expression of TrpV4 and GFAP in EG and during different EG stages.
Unilateral chronic elevation of IOP was induced in 8 adult NHPs by laser treatment to the trabecular meshwork. Peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by SDOCT. EG stage was defined as RNFLT % loss, early (EEG; RNFLT <20% baseline; n=4) and advanced (AEG; RNFLT >20% baseline; n=4) EG animals. Sagittal ON cryosections were prepared for IHC staining with GFAP and TrpV4 antibodies. Whole ON sections were montaged using custom software, the laminar and retrolaminar ON regions were quantified as integrated density and compared to CTL.
(1)Control (CTL): GFAP presents as thread-like labeling parallel to the ON bundles through-out the retrolaminar. Patterned similarly, TrpV4 co-localizes with the GFAP expression. (2) EEG:(a) GFAP shows a 33% reduction in the laminar with no apparent change in the retrolaminar expression. (b) TrpV4 shows a laminar 20% decrease and a 43% retrolaminar increase. GFAP and TrpV4 co-localize and present parallel to the ON bundles. (3) AEG:(a) GFAP shows a laminar 16% decrease and a retrolaminar 56% increase. (b) TrpV4 shows a laminar 21% decrease and a retrolaminar 111% increase. (4): EEG + AEG: combining both stages enables the use of non-parametric statistics. (a) GFAP shows a 24% (fig. 1; p=0.07) reduction in the laminar. (b) TrpV4 shows a significant 77% increase (fig. 2; p=0.01) in the retrolaminar.
GFAP expression does not change significantly in the retrolaminar during EG. However, in the laminar we see an immediate GFAP decrease in EEG, continued in AEG; implying astrocyte deactivation within the laminar is an early step in EG. Conversely, TrpV4 shows no significant change in the laminar, but there is a distinct increase within the retrolaminar compared to CTL. Furthermore, this TrpV4 expression increases during EEG and amplified in AEG. The specific role of TrpV4 and the physiological reason for these changes on blood flow remain under investigation.
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