Research reportThe patterns of retinal ganglion cell death in hypertensive eyes
Introduction
Visual field loss in human hypertensive eye is a result of retinal ganglion cell (RGCs) death. Mechanisms by which the retinal ganglion cells die in hypertensive eyes are not clear. Death is thought to follow either apoptotic and /or necrotic pathway. Selective death of retinal ganglion cells in hypertensive eye may be due to direct compressive effects on the optic nerve causing axonal damage [7]. Various experiments have shown the interruption of retrogradely transported material to the RGCs from the brain at the lamina cribrosa. It has been postulated that loss of trophic factor available to the retina causes cell death. Other mechanisms include intracellular electrolyte imbalance and microglial phagocytosis 3, 11, 18. Recently, Dreyer et al. [6]showed elevated glutamate levels in vitreous body of humans and monkeys with hypertensive eyes, which may also be involved in causing cell death.
We have recently described a model in rats in which we induce elevation of intraocular pressure by episcleral vein cauterization [12]. After elevated pressure induction or optic nerve cut, cell death was studied by using `terminal transferase method' which indicated apoptotic mode of cell death of retinal ganglion cells 11, 12, 17. Cell death after axotomy peaks at day 7 whereas, small numbers of cells continue to die over the period of time in hypertensive eyes. After episcleral vein cauterization there is minimum damage to ocular tissues and no vascular abnormalities were detected using planar ophthalmoscopy [12]. Cell death after ischemia in the retina is sudden and extensive like the one reported by Selles-Navarro et al. in rat [20]. They reported that 75 to 95% of retinal ganglion cells die after 90 to 120 min of ischemia over a period of 30 days. Examination of the temporal mid-peripheral region of the monkey retina in hypertensive eyes revealed that large retinal ganglion cells were more vulnerable to damage than smaller sized cells, and that large axons in corresponding areas of the optic nerve were affected 13, 14. Despite the existence of various hypotheses, the exact pattern of RGC death in hypertensive eyes has not been reported for the entire retina. It is also unclear whether the cell death is uniform throughout the extent of the rat retina. Here, we determined the patterns in which retinal ganglion cells die after elevated IOP in the entire retina.
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Material and methods
Thirty Wistar rats (250–325 g) were used. All rats were maintained in accordance with institutional humanitarian regulations. Rats were anesthetized with an intraperitoneal injection of a solution containing ketamine (Ketaset; 40 mg/kg), xylazine (Rompun; 8 mg/kg), and acepromazine (Pormace; 1.2 mg/kg). Their heads were mounted on a stereotactic apparatus and Fast blue (0.05%) in 0.1 M phosphate buffered saline (PBS) pH 7.4, was injected into 9 mirror image sites across each superior colliculus
Results
Mean IOP in normal control eye was 13.2 mmHg. It ranged between 11–14 mmHg in different rats. Cauterization of two episcleral veins elevated the intraocular pressure in experimental rats, which ranged from 21–23 mmHg, as described previously by us [21]. The IOP has been shown to be in this range by other investigators as well 16, 19. The pneumatonometer used in our study measures IOP through applanation tonometry. A pneumatic sensor touches the surface of anesthetized cornea. As the
Discussion
The similarities in the anterior segment blood supply and the aqueous outflow between rats and primates are important in creating models for studying the effects of increase intraocular pressure [9]. The death of retinal ganglion cells in hypertensive eyes is the known cause of visual field deficits. Various scotomas have been reported in glaucomatous patients that do indicate a pattern to the death of the RGCs leading to corresponding patterns of visual field loss. Earlier human studies have
Acknowledgements
This work was supported by NIH Grant EY-11295.
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