Differential dendritic shrinkage of and retinal ganglion cells in cats with chronic glaucoma.

Abstract

PURPOSE. To study changes in the dendritic morphology of retinal ganglion cells (RGCs) in cats with experimental chronic glaucoma. METHODS. Chronic elevation of intraocular pressure (IOP) was produced by injecting endogenous ghost red blood cells into the unilateral anterior chamber of the feline eyes for 1 month. The morphologic features of retrograde-labeled RGCs by bilateral injection of horseradish peroxidase (HRP) into layers A and Aa1 of the lateral geniculate nucleus (LGN) were examined and compared between the normal and glaucomatous eyes. Nissl staining was used for measuring the change in cell density in the retina and the LGN. RESULTS. Quantitative analysis of 720 labeled ␣ and ␤ type RGCs showed that the cell density, body size, maximum dendritic field radius, total dendritic length, and number of branch bifurcations of dendrites decreased significantly in glaucomatous eyes compared with normal ones. The cell loss and shrinkage of dendrites in ␣ type ganglion cells in the retina was more pronounced than that in ␤ type cells. The cell density of all kinds of cells in the retina and LGN monotonically declined with time while IOP was elevated, and cell loss was more significant in large cells than in small ones. G laucoma is the most common cause of blindness except for cataracts. In most cases, glaucoma is characterized by an elevation of intraocular pressure (IOP), progressive changes in morphology of the optic disc and retinal axon layer, and visual field defects. Eventually, it makes the eye blind by killing retinal ganglion cells (RGCs). Many studies have shown that glaucoma and chronic elevation of IOP cause degeneration in the optic nerve fibers 1-4 and progressive loss of retinal ganglion cells. 4 -6 Weber et al. In the cat's retina, ␣ and ␤ ganglion cells are classically defined as distinct morphologic types that correspond to physiological Y-and X-type cells, respectively. Y (or ␣) cells have the largest soma, the largest dendritic field area, and the thickest dendrites and preferentially respond sensitively to stimuli of low contrast, low spatial frequency, and fast-moving patterns. In contrast, X (or ␤) cells have a medium soma, the smallest dendritic field area, and a bushy dendritic arbor and are sensitive to stimuli of higher contrast, fine structure, and relatively low velocity of motion. 10 -14 Both Y and X RGCs project separately to Y-and X-type relay cells in layers A and A1 of the dorsal lateral geniculate nucleus (LGN) and form the parallel pathway of visual information processing in the cat, 12-14 similar to the magno-and parvocellular pathways in the monkey's visual system. It is well-documented in monkeys with chronic glaucoma that large RGCs are more seriously damaged than small cells. 2-4 However, previous studies in our laboratory have demonstrated that in the cat, the Y-type ganglion cells in the retina and relay cells in the LGN are more tolerant than X cells to brief elevations of IOP. METHODS Animal Model of Chronic Glaucoma Fourteen adult cats weighing between 2 kg and 2.7 kg were used as experimental models of glaucoma. Their eyes were tested to ensure ophthalmic health. All the procedures for production of chronic elevated IOP were conducted according to the description by Quigley and Addicks. 18 The glutaraldehyde-fixed autogenous red cells in saline (1:1 in volume) of 0.3 mL was injected into the anterior chamber of the unilateral eye of a cat when another syringe was used to drain off the same volume of aqueous humor. The contralateral eye of each cat was used as the control. The IOP of each eye was repeatedly measured using a Schiotz tonometer in cats under ketamine anesthesia. The From th