Swelling and Loss of Photoreceptors in Chronic Human and Experimental Glaucomas

Abstract

To determine whether outer retinal changes occur in chronic, presumed primary open-angle glaucoma (POAG). Methods: The outer retinas from 128 human eyes with a diagnosis of chronic glaucoma (presumably POAG in most cases) and 90 control eyes were examined histologically by 3 masked observers for photoreceptor swelling and loss. Retinas from 9 rhesus monkeys with glaucoma induced experimentally by laser trabecular destruction were compared with 7 fellow (control) eyes. The mean pressure elevations in the eyes with laser trabecular destruction ranged from 26.6 to 53.6 mm Hg with durations varying from 7 to 33 weeks. Results: Swelling of the red-and green-sensitive cones was observed in a statistically significantly greater proportion of human eyes with presumed POAG compared with the control eyes. Patchy loss of red/green cones and rods was also found in some of the glaucomatous retinas. In a subset of the human eyes with end-stage disease, cone swelling was a variable finding. Although no photoreceptor loss was found in the 9 monkey eyes with experimental glaucoma, 8 had swelling of their red/green cones that was remarkably similar to that seen in the human eyes. Swelling was not present in any of the control monkey eyes. Conclusions: The photoreceptors are affected by chronically elevated intraocular pressure. Clinical Relevance: These findings may explain some of the abnormalities of color vision and the electrophysiological effects that have been observed in patients with POAG.

Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging

“…There is emerging evidence from histological, electrophysiological, and OCT studies that the processes involved in glaucomatous damage could also involve other neuronal cells such as amacrine cells, 51 bipolar cells, 50,52 horizontal cells, 53 and photoreceptors. 52,[54][55][56][57] Therefore, reduced mass tissue extraction of oxygen within the retinal layers would support our explanation of retinal venous hyperoxia.…”

Premise and Prediction???How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

“…While glaucomatous damage to the visual system likely includes important pathophysiologies within the retinal ganglion cell (RGC) body 27-32 , photoreceptors [33][34][35][36][37] The ONH tissues make up a dynamic environment wherein 1.2 to 2.0 million retinal ganglion cell axons converge, turn, and exit the eye through the inner (Bruch's Membrane opening) and outer (scleral) portions of the neural canal (Figure 1). Within the scleral portion of the canal, the bundled axons pass, through a 3-dimensional (3D) meshwork of astrocyte-covered, capillary containing, connective tissue beams known as the lamina cribrosa (Figure 1).…”

“…While glaucomatous damage to the visual system likely includes important pathophysiologies within the retinal ganglion cell (RGC) body [27][28][29][30][31][32] , photoreceptors [33][34][35][36][37] , lateral geniculate body [38][39][40] and visual cortex 40 , strong evidence suggests that damage to the retinal ganglion cell axons within the lamina cribrosa of the ONH [41][42][43][44][45][46] is the central pathophysiology underlying glaucomatous vision loss. Recent studies in the monkey [45][46][47][48][49][50] and rat [51][52][53] support the importance of the ONH, by describing profound alterations within the prelaminar, laminar and peripapillary scleral tissues of the ONH at the earliest detectable stage of experimental glaucoma.…”

The pro-inflammatory role of high-mobility group box 1 protein (HMGB-1) in photoreceptors and retinal explants exposed to elevated pressure

“…Recent studies suppose diminished expression of opsins in ischemic pathologies, eg, owing to choroidal insufficiency related to increased levels of IOP. 9,10 The high-mobility group protein B1 (HMGB-1), which is expressed ubiquitously in mammalian cells, is a highly conserved nuclear protein that participates in DNA replication, recombination, transcription, and repair. [11][12][13] The role of HMGB-1 in the central nervous system is barely understood.…”