Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Muller cells. These data suggest that VEGF/VPF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization.

https://www.pnas.org/content/pnas/92/3/905.full.pdf

Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization

We reviewed research on retinal oxygen (O2) distribution and use, focusing on O2 microelectrode studies in animals with circulatory patterns similar to those of humans. The inner and outer halves of the retina are different domains in terms of O2. Understanding their properties can suggest mechanisms of and therapies for retinal diseases. Inner retinal PO2 averages about 20 mm Hg. Effective O2 autoregulation of the retinal circulation ensures that inner retinal PO2 is relatively uninfluenced by systemic hypoxia and hyperoxia and increased intraocular pressure in healthy animals. Failures of the retinal circulation lead to tissue hypoxia that underlies the vasoproliferation in diabetic retinopathy and retinopathy of prematurity. Choroidal blood flow is not regulated metabolically, so systemic hypoxia and elevated intraocular pressure lead to decreases in choroidal PO2 and photoreceptor O2 consumption. The same lack of regulation allows choroidal PO2 to increase dramatically during hyperoxia, offering the potential for O2 to be used therapeutically in retinal vascular occlusive diseases and retinal detachment.

/pdf/retinal-oxygen-fundamental-and-clinical-aspects-k1txi4b80h.pdf

Retinal Oxygen: Fundamental and Clinical Aspects

Regulation of retinal blood flow in health and disease

Diabetic macular edema: pathogenesis and treatment.

These experiments were done to investigate the effects of light and darkness on the oxygenation of the retina in anesthetized cats. Measurements were made with double-barreled oxygen microelectrodes capable of recording both oxygen tension (PO2) and local voltages. Diffuse white illumination presented to a dark-adapted retina led to an increase in PO2 of up to 30 mmHg in the outer half of the retina. Changes were maximal at approximately 75% depth, corresponding to the outer nuclear layer. No change or decrease in PO2 was observed in the inner retina. Light-evoked increases in outer retinal PO2 were graded with the duration and strength of illumination, and were maximal in response to 60 s of illumination at rod saturation. For these stimuli, the increase at the onset of illumination was slower (average half-time, 12.2 s) than the recovery at the end of illumination (average half-time, 5.9 s), but for stimuli above rod saturation, PO2 recovered much more slowly. The profile of PO2 was measured during electrode penetration and withdrawal and during light and dark adaptation. Dark-adapted profiles were characterized by a minimum PO2 of nearly 0 mmHg at depths of 65-85%, and a steep gradient from the minimum to the choroid. During light adaptation at rod saturation, PO2 was elevated in the outer half of the retina and the minimum was eliminated. Fits of the profiles to a one-dimensional model of oxygen diffusion indicated that light reduced the oxygen consumption of the outer retina to approximately 50% of its dark-adapted value.

https://rupress.org/jgp/article-pdf/88/4/521/1246591/521.pdf

Effects of Light and Darkness on Oxygen Distribution and Consumption in the Cat Retina

A large area of the posterior pole of the retina of the miniature pig was photocoagulated, and 2-3 wk later the PO2 in the preretinal vitreous was mapped with O2-sensitive microelectrodes. In the control retina, the PO2 was highly heterogeneous being much higher close to an artery than opposite an intervascular zone. After photocoagulation, PO2 opposite an intervascular zone was found to be significantly increased. A quantitative histologic analysis showed that in the photocoagulated areas more than 28% of the outer retina was destroyed. The authors conclude from these results that photocoagulation, by partially destroying the pigment epithelium-photoreceptor complex, causes an increase of the oxygenation of the retina.

Effect of laser photocoagulation on oxygenation of the retina in miniature pigs.

Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy.

Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs

Purpose:We describe a retinal endovascular fibrinolysis technique to directly reperfuse experimentally occluded retinal veins using a simple micropipette.Methods:Retinal vein occlusion was photochemically induced in 12 eyes of 12 minipigs: after intravenous injection of 10% fluorescein (1-mL bolus),

The rationale of retinal endovascular fibrinolysis in the treatment of retinal vein occlusion: from experimental data to clinical application.

Purpose To evaluate the effect of anti‐VEGF drugs and steroids on the inner blood‐retinal barrier (BRB) function after experimental branch retinal vein occlusion (BRVO) in rats. The integrity of the barrier is related to the expression of occludins by retinal endothelial cells.

N Gilodi

Papers

Effect of laser photocoagulation on oxygenation of the retina in miniature pigs.

Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy.

Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs

The rationale of retinal endovascular fibrinolysis in the treatment of retinal vein occlusion: from experimental data to clinical application.

Effect Of Anti-vegf Drugs And Steroids On The Inner Blood-retinal Barrier, After Experimental BRVO In Rats