The long-term objectives of this work are to understand aspects of the retinal microenvironment related to oxygen and pH, and how these relate to energy metabolism and function of the mammalian retina in vivo. While this work will be done in animals, it is particularly relevant to blinding diseases that affect the relationships between the circulation and retinal neurons in humans. During the next project period, our main interests are in diabetic retinopathy, retinal detachment, and retinal arterial occlusive disease. However, the results will also provide fundamental information that may be relevant to other types of retinal dysfunction. The proposed work will be done primarily on intact anesthetized cats, since their retina provides a good model for much of the human retina. The techniques are primarily to use oxygen and pH sensitive microelectrodes to map out retinal oxygen levels, pH and electrical activity (the electroretinogram) with high spatial and temporal resolution, as we have done previously under other experimental conditions. Following the measurements, mathematical modeling of diffusion will be used to extract metabolic parameters that are not apparent from the measurements alone, and to perform simulations of situations that may not be amenable to experimentation. Some measurements of retinal histology will also be made. The project has 5 specific aims. 1) We will study intraretinal oxygenation following photocoagulation, because the mechanism by which photocoagulation blocks neovascularization is still unclear. 2) We will use information about oxygenation after photocoagulation from specific aim 1 to create an appropriate two-dimensional diffusion model of this situation, with the hope of providing a better rationale for the density and size of lesions designed to treat retinopathy. 3) We will study retinal oxygenation in the detached retina in order to understand the basis for the protective effect of hyperoxia in retinal detachment, which has been shown recently in cats. 4) We will study pH after retinal arterial occlusion, to understand the potential role of acidosis in damaging the retina. 5) We will investigate the influence of anesthesia on the metabolic measurements we make, and will study metabolic differences between the cat and primate retinas.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Dudley, Peter A
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Northwestern University at Chicago
Biomedical Engineering
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United States
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Linsenmeier, Robert A; Zhang, Hao F (2017) Retinal oxygen: from animals to humans. Prog Retin Eye Res 58:115-151
Lee, Christine J; Smith, Jennifer H; Kang-Mieler, Jennifer J et al. (2011) Decreased circulation in the feline choriocapillaris underlying retinal photocoagulation lesions. Invest Ophthalmol Vis Sci 52:3398-403
Wang, Shufan; Birol, Gulnur; Budzynski, Ewa et al. (2010) Metabolic responses to light in monkey photoreceptors. Curr Eye Res 35:510-8
Budzynski, Ewa; Smith, Jennifer H; Bryar, Paul et al. (2008) Effects of photocoagulation on intraretinal PO2 in cat. Invest Ophthalmol Vis Sci 49:380-9
Wang, Shufan; Linsenmeier, Robert A (2007) Hyperoxia improves oxygen consumption in the detached feline retina. Invest Ophthalmol Vis Sci 48:1335-41
Chung, Christina K; Linsenmeier, Robert A (2007) Effect of carbogen (95% O2/5% CO2) on retinal oxygenation in dark-adapted anesthetized cats. Curr Eye Res 32:699-707
Padnick-Silver, Lissa; Derwent, Jennifer J Kang; Giuliano, Elizabeth et al. (2006) Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration. Invest Ophthalmol Vis Sci 47:3683-9
Derwent, Jennifer J Kang; Padnick-Silver, Lissa; McRipley, Monique et al. (2006) The electroretinogram components in Abyssinian cats with hereditary retinal degeneration. Invest Ophthalmol Vis Sci 47:3673-82
Padnick-Silver, Lissa; Linsenmeier, Robert A (2005) Effect of hypoxemia and hyperglycemia on pH in the intact cat retina. Arch Ophthalmol 123:1684-90
Padnick-Silver, Lissa; Linsenmeier, Robert A (2003) Effect of acute hyperglycemia on oxygen and oxidative metabolism in the intact cat retina. Invest Ophthalmol Vis Sci 44:745-50

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