Abstract
Purpose:
To determine the relationship of GFAP upregulation in Müller cells to elevated intraocular pressure (IOP) and the presence of RGCs in experimental glaucoma and axotomy in monkeys.
Methods:
Immunohistochemistry for GFAP was performed on the retinas of both eyes of 13 monkeys. In all of the animals, the right eye was the experimental eye and the left eye was the untreated control. 6 cynomolgus macaques had glaucoma induced by laser trabecular destruction (LTD) from 3 to 9 years prior to sacrifice. The mean IOPs during the last 14 months of life varied from 23 to 54 mmHg in the treated eyes (43 mean for all animals). 4 cynomolgus macaques had inferior hemiretinal endodiathermy axotomy (HEA) either 3 or 4 months prior to sacrifice with no elevation in IOP (Dashek et al, IOVS, 2013;54:3479). 3 rhesus macaques had HEA axotomy and 9.5 months later underwent LTD (mean IOP varied from 34 to 56 mmHg) and were sacrificed 4.5 months after LTD.
Results:
Although the retinal astrocytes and optic nerve oligodendrocytes were strongly positive for GFAP, there was little or no upregulation of GFAP in the Müller cells in any of the 6 eyes with chronic glaucoma. Likewise, there was no upregulation of GFAP in the Müller cells of any of the 4 eyes that underwent HEA alone. However, there was marked Müller cell GFAP upregulation in both the superior (no axotomy) and inferior (axotomy) areas of all 3 eyes that had HEA plus 4.5 months of experimental glaucoma.
Conclusions:
Müller cell GFAP upregulation is not dependent on the presence of RGCs since upregulation occurred even though RGCs were essentially absent from the axotomized areas of retina in the 3 HEA animals with elevated IOP. However, elevated IOP alone is not a sufficient condition for sustained Müller cell GFAP upregulation because it was not readily apparent in any of the 6 eyes with chronic glaucoma. One possibility is that Müller cell GFAP upregulation is the result of retinal ischemia, such as from decreased choroidal blood flow. Compensatory mechanisms, e.g. increased blood flow or decreased retinal oxygen need due to retinal cell death and/or lowered metabolism, may have allowed the Müller cell GFAP to return to nearly normal levels in the eyes with chronic glaucoma.
Keywords: 568 intraocular pressure •
603 Muller cells •
699 retinal glia