Vascular and Glial Changes in the Retrolaminar Optic Nerve in Glaucomatous Monkey Eyes

Abstract

Vascular and glial changes of the retrolaminar optic nerve were studied in monkey eyes with increased intraocular pressure (IOP) from 1 to 4 years and with different stages of optic nerve atrophy. In histological cross-sections of retrolaminar optic nerves of 11 rhesus and 6 cynomolgus monkeys the entire area, number of axons and vessels and area of pial septa were quantitated and three different kinds of nerve degeneration classified. Ultrathin sections of these different stages were performed and the number of open and occluded vessels was determined. In addition, in cynomolgus monkey optic nerves immunohistochemical staining for αB-crystallin, glial fibrillary acidic protein (GFAP) and vimentin was performed. Even in animals with the same duration of glaucoma and comparable mean IOP values the axon degeneration varied considerably. Independently of axon loss the number of capillaries in the rhesus monkeys remained constant, whereas there was a slight decrease in the cynomolgus monkeys. Some of the vessels, especially in the most severely damaged regions, were occluded. The density of glial cells increased whereas the total number remained nearly constant. In control sections all astrocytes stained for GFAP and αB-crystallin. In the glaucomatous optic nerves the density of αB-crystallin- and GFAP-positive cells was significantly increased. The vascular reaction in the retrolaminar glaucomatous optic nerves differs from that described in the prelaminar region. We assume that in the postlaminar region in areas with diminished nutritional needs vessels occlude and finally degenerate.

Functional rescue of experimental ischemic optic neuropathy with αB-crystallin

“…25,26 The upregulation of aBC, a molecular chaperone important in retinal ischemia, experimental glaucoma, and central nervous system inflammatory disease, [14][15][16]27 following experimental AION was consistent with its role as a endogenous protective mechanism. [28][29][30] Consistent with this idea, early, 3-day intravenous aBC treatment dampened post-AION microglial activation, although it did not impact fVEP responses on days 1-2.…”

Distribution of αB-Crystallin in the Central Retina and Optic Nerve Head of Different Mammals and its Changes during Outer and Inner Retinal Degeneration

“…Ad 3. Increase of ABC in glaucomatous optic nerves was reported [8,10], but a precise localization has not been described so far. Interestingly, the mouse glaucoma model is not suitable for this type of investigations since ABC seems to play no major role in the mouse eye pathology.…”

“…In age-related macular degeneration ABC accumulation was described in drusen [43][44][45] and recent interest is focused on this protein in the retinal pigmented epithelium [46,47]. Increase of ABC was reported in the glaucomatous retrolaminar optic nerve [8] and trabecular meshwork [48] and in a mouse model of outer retinal degeneration [12]. In this study, several models with chronic retinal destruction were studied concerning their distribution of ABC.…”

“…For this reason it is considered to be a useful marker in a variety of neurodegenerative diseases [9]. Concerning ocular pathologies, an increase in ABC was described in the retrolaminar optic nerve of glaucomatous monkey eyes [8]. In vitro studies confirmed the increase of ABC in human optic nerve head astrocytes exposed to elevated hydrostatic pressure [10].…”

“…Hsp25 in rodents and birds) [1,2], ABC is a highly conserved protein that exists in nearly any species examined [3][4][5][6]. In previous work we could show that ABC is present in the retrolaminar optic nerve of numerous species including human, monkey, cow, pig, rat, and mouse [7,8]. The amount of ABC showed species differences but was homogenous within different age groups of a single species.…”