Glial Cell Contribution to Basal Vessel Diameter and Pressure-Initiated Vascular Responses in Rat Retina

Abstract

PurposeThe purpose of this study was to test the hypothesis that retinal glial cells modify basal vessel diameter and pressure-initiated vascular regulation in rat retina.MethodsIn rats, L-2-aminoadipic acid (LAA, 10 nM) was intravitreally injected to inhibit glial cell activity. Twenty-four hours following injection, retinal glial intracellular calcium (Ca2+) was labeled with the fluorescent calcium indicator Fluo-4/AM (F4, 1 mM). At 110 minutes after injection, intraocular pressure (IOP) was elevated from 20 to 50 mm Hg. Prior to and during IOP elevation, Ca2+ and retinal vessel diameter were assessed using a spectral-domain optical coherence tomography/confocal scanning laser ophthalmoscope. Dynamic changes in Ca2+ and diameter from IOP elevation were quantified. The response in LAA-treated eyes was compared with vehicle treated control eyes.ResultsL-2-Aminoadipic acid treatment significantly reduced F4-positive cells in the retina (LAA, 16 ± 20 vs. control, 55 ± 37 cells/mm2; P = 0.02). Twenty-four hours following LAA treatment, basal venous diameter was increased from 38.9 ± 3.9 to 51.8 ± 6.4 μm (P < 0.0001, n = 20), whereas arterial diameter was unchanged (from 30.3 ± 3.5 to 30.7 ± 2.8 μm; P = 0.64). In response to IOP elevation, LAA-treated eyes showed a smaller increase in glial cell Ca2+ around both arteries and veins in comparison with control (P < 0.001 for both). There was also significantly greater IOP-induced vasoconstriction in both vessel types (P = 0.05 and P = 0.02, respectively; n = 6 each).ConclusionsThe results suggest that glial cells can modulate basal retinal venous diameter and contribute to pressure-initiated vascular responses.

Downregulation of Retinal Connexin 43 in GFAP-Expressing Cells Modifies Vasoreactivity Induced by Perfusion Ocular Pressure Changes

“…We previously showed that the pharmacologic inhibition of glial activity increased the basal venular diameter and compromised the responses of both the arterioles and the venules to a rapid increase in the IOP. 11 These data are consistent with the possibility that glial cells participate in the maintenance of both basal venular tone and the regulation of vascular resistance in response to changes in the local pressure environment. However, the rapid IOP elevation used in our previous study can introduce an abrupt compression of the vessels, which may complicate interpretation.…”

“… 10 We previously demonstrated that perivascular glia in rat retina were activated in response to acute IOP elevation, as evidenced by increased intracellular calcium concentration. 11 Pharmacologic inhibition of glial activity significantly blunted calcium activation and impaired the capacity for the vasculature to respond to IOP elevation. This finding is consistent with the results of Kim et al, 9 which showed that the inhibition of astrocyte activation (decreased calcium activity) attenuated compensatory vascular responses to an acute, phenylephrine-induced elevation of the systemic blood pressure (BP).…”

“…Given that a change in either of those pressures can impact transmural pressure, one might expect the glia to modulate the vascular responses to BP-lowering as they are known to do during IOP elevation. 11 Thus, a key aim of this study is to compare the effect of glial cells on retinal vascular responses to a decreased OPP achieved via IOP elevation or an equivalent decrease in the BP. Because both IOP elevation and BP lowering decrease the OPP and have been considered to be risk factors for glaucoma, 12 , 13 the results may help to better define the vasopathology of glaucoma and other diseases.…”

Short‐time effect of intravitreal injections on retinal vascular oxygenation and vessel diameter in patients with diabetic macular oedema or neovascular age‐related macular degeneration

“…In addition, endothelial dysfunction may contribute to an imbalance of diameter regulation in diabetes (Pemp et al 2009). Recent evidence also suggests that retinal glial cells are capable of sensing the reduction in perfusion pressure and contribute to the maintenance of vessel diameters (Li et al 2017). Since glial cells are affected early in the diabetic retina and continue to degenerate along with retinal ganglion cells (Coughlin et al 2017), neuroretinal damage may be another important factor in disturbed retinal vascular autoregulation.…”

Response of the Trilaminar Retinal Vessel Network to Intraocular Pressure Elevation in Rat Eyes

“…Consistently, in response to a relatively low magnitude IOP elevation (10-40 mm Hg), vasodilation occurs to prevent a drop in blood flow. 8,9 When IOP elevation reaches 60 to 70 mm Hg, autoregulation mechanisms are overwhelmed resulting in forceful compression of inner retinal vessels and attenuation of blood flow. 10 Although many studies have documented autoregulation-induced changes in the larger surface vessels, few have considered the smaller vessels.…”