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Samir Jabbour, Michael G Quigley; Diabetic retinopathy: what happens before VEGF?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2120. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Today, VEGF is recognized as playing an important role in the genesis and evolution of diabetic retinopathy. Several clinical conditions including myopia, retinitis pigmentosa (RP) and growth hormone (GH) deficiency have been associated with protection of the retina from diabetic retinopathy. A study by Suzuma et al. (Diabetes, 2001) showed that cyclic stretch within retinal capillaries induces the expression of VEGF and that decreasing this stretch returns VEGF production to baseline levels. We hypothesize that these previously mentioned protective conditions result in a decreased hydrostatic pressure and stretch at the level of capillaries, down regulating the expression of VEGF and hence mitigating the development of diabetic retinopathy.
Using a previously described pressure attenuation index (PAI) (Quigley et al., Archives of Ophthalmology, 1999), the relative capillary hydrostatic pressure in normotensives (120/80 mmHg), hypertensives (150/100 mmHg), and in the above-mentioned protective conditions was calculated. This index combines the Murray law and Poisseuille’s principle and shows that pressure in a given vascular system is attenuated in proportion to its length and inversely proportional to its diameter.
Hypertensives have a 4mmHg increase in intraluminal capillary pressure compared to normotensives. An increase in the eye’s myopia to -6 diopters, which is equivalent to a 15% increase in retinal vessel length, would result in a 4.4 mmHg decrease in the capillary pressure over normal. In RP, an arteriolar narrowing of 69% from normal would decrease capillary pressure by 13 mm Hg over normal. In GH deficiency, decreased flow due to narrowing of blood vessels would result in a capillary pressure of 7.5 mm Hg less than normal.
Protective conditions in diabetic retinopathy lead to a calculable decreased intraluminal capillary hydrostatic pressure which would decrease capillary stretch and VEGF production. A lowering of the end-arteriolar pressure could be a common pathway to decreasing VEGF production and mitigating the effects of diabetes on the microvessels, and could be considered as a goal towards which therapeutic modalities are directed.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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