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Alena Z. Minton, Nitasha Phatak, Brett Mueller, Hai-Ying Ma, Ming Jiang, Shaoqing He, Raghu Krishnamoorthy; Neurodegenerative Effects of Endothelin B Receptors in a Rodent Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2654.
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Recent observations suggest the involvement of ETB receptors in the pathogenesis of glaucoma. This study was aimed at investigating whether there are any changes in the expression of ETB receptor in vivo in the Morrison’s elevated intraocular pressure (IOP) model of glaucoma in rats.
Brown Norway rats were subjected to IOP elevation following which they were sacrificed. Retinas were sectioned and stained for ETB receptor expression by immunohistochemistry. Colocalization of ETB receptor immunostaining was performed using an antibody to neuritin, a selective marker of RGCs. In a separate study, adult ETB+/+ and ETB-/- transgenic Wistar rats were used for retrograde labeling of retinal ganglion cells (RGCs) with Fluoro-gold. Following retrograde labeling, IOP was elevated in one eye using the Morrison’s method (injection of hypertonic saline through episcleral veins), while the contralateral eye served as control. After IOP was elevated, rats were maintained for 2 to 4 weeks and sacrificed. Fluoro-gold labeled retinas were isolated, flat-mounted, photographed using Zeiss LSM-510 confocal microscope, and labeled RGCs were counted.
Immunohistochemical analysis showed that IOP elevation caused increased expression of ETB receptor in the RGCs, inner plexiform layer (IPL) and inner nuclear layer (INL). Increased colocalization of ETB receptors with neuritin was identified mainly in RGCs and IPL in rat eyes with elevated IOP. IOP elevation for 2 to 4 weeks in ETB+/+ transgenic rats caused appreciable loss of RGCs which was attenuated in ETB-/- transgenic rats.
Increased intraocular pressure caused increased ETB receptor expression possibly through pressure-related mechanism. ETB receptors may contribute to retinal ganglion cell death as seen in glaucoma.
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