Long-lasting impairments in rodent oxygen-induced retinopathy measured by retinal vessel density and visual function
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In mild or moderate retinopathy of prematurity (ROP), retinal vessels undergo obliteration, proliferation, and regression. Despite complete regression of vessel abnormalities, a variety of visual impairments have been reported. Rodent oxygen-induced retinopathy (OIR) is widely used as a model to study ROP. However, the long-term changes of OIR model remain unclear. The aim of this study is to examine long term changes of retinal vessel and visual function in a rodent OIR model resembling human mild or moderate ROP. In this study, after subjecting the animals to 80% oxygen (O2) for 5–7 d, the retinal vessel density at postnatal day 12 (P12) was approximately 30% lower than that in the age-matched control, but this difference was not significant between the groups. Vessel abnormalities, such as vessel tortuosity, neovascular tufts, and the number of vessels protruding into the vitreous, peaked between P17 and P20. Despite the regression of many abnormalities, vessel density in the OIR group was 36% and 32% lower than that in the control animals at 6 weeks and 4 months, respectively. The visual acuity and contrast sensitivity were impaired in the OIR group when measured at 2, 3 and 4 months. Therefore, the rodent OIR model exhibited long-lasting reduction in retinal vessel density and visual impairments, similar to those observed in mild or moderate human ROP. This study suggests that the rodent OIR model can be used to explore possible interventions for mild and moderate human ROP.
Keywordsoxygen-induced retinopathy vessel plasticity visual acuity contrast sensitivity rat
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This work was supported by the National Natural Science Foundation of China Key Project (31030036) to SH, a National Natural Science Foundation of China Project (81570863) and Science and Technology Supporting Program by Department of Science and Technology, Sichuan Province (2016SZ0024) to FL. We would like to thank Ms. Jiaying Ju for technical support.
- Arámbulo, O., Dib, G., Iturralde, J., Duran, F., Brito, M., and Fortes Filho, J.B. (2015). Intravitreal ranibizumab as a primary or a combined treatment for severe retinopathy of prematurity. Clin Ophthalmol 19, 2027–2032.Google Scholar
- Connor, K.M., Krah, N.M., Dennison, R.J., Aderman, C.M., Chen, J., Guerin, K.I., Sapieha, P., Stahl, A., Willett, K.L., and Smith, L.E.H. (2009). Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc 4, 1565–1573.CrossRefGoogle Scholar
- Cryotherapy for Retinopathy of Prematurity Cooperative Group. (1988). Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Arch Ophthalmol 106, 471–479.Google Scholar
- Dembinska, O., Rojas, L.M., Chemtob, S., Lachapelle, P. (2002). Evidence for a brief period of enhanced oxygen susceptibility in the rat model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 43, 2481–2490.Google Scholar
- Dobson, V., Quinn, G.E., Abramov, I., Hardy, R.J., Tung, B., Siatkowski, R. M., Phelps D.L. (1996). Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYOROP study. Invest Ophthalmol Vis Sci 37, 2467–2474.Google Scholar
- Gibson, D.L., Sheps, S.B., Uh, S.H., Schechter, M.T., McCormick, A.Q. (1990). Retinopathy of prematurity-induced blindness: birth weightspecific survival and the new epidemic. Pediatrics 86, 405–412.Google Scholar
- Hansen, R.M., Fulton, A.B. (2000). Background adaptation in children with a history of mild retinopathy of prematurity. Invest Ophthalmol Vis Sci 41, 320–324.Google Scholar
- Penn, J.S., Henry, M.M., Wall, P.T., Tolman, B.L. (1995). The range of PaO2 variation determines the severity of oxygen-induced retinopathy in newborn rats. Invest Ophthalmol Vis Sci 36, 2063–2070.Google Scholar
- Penn, J.S., Tolman, B.L., Henry, M.M. (1994b). Oxygen-induced retinopathy in the rat: relationship of retinal nonperfusion to subsequent neovascularization. Invest Ophthalmol Vis Sci 35, 3429–3435.Google Scholar
- Penn, J.S., Tolman, B.L., Lowery, L.A. (1993). Variable oxygen exposure causes preretinal neovascularization in the newborn rat. Invest Ophthalmol Vis Sci 34, 576–585.Google Scholar
- Reisner, D.S., Hansen, R.M., Findl, O., Petersen, R.A., Fulton, A.B. (1997). Dark-adapted thresholds in children with histories of mild retinopathy of prematurity. Invest Ophthalmol Vis Sci 38, 1175–1183.Google Scholar
- Reynaud, X., Vallat, M., Vincent, D., Dorey, C.K. (1991). Protective effect of the Ginkgo biloba extract in the rat model of retinopathy of prematurity (ROP). Invest Ophthalmol Vis Sci 32. 1147.Google Scholar
- Ridler, T.W., Calvard, S. (1978). Picture thresholding using an iterative selection method. In: IEEE Systems, Man, and Cybernetics Society 8, 630–632.Google Scholar
- Smith, L.E., Wesolowski, E., McLellan, A., Kostyk, S.K., D’Amato, R., Sullivan, R., et al. (1994). Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35, 101–111.Google Scholar
- Ventresca, M.R., Gonder, J.R., Tanswell, A.K. (1990). Oxygen-induced proliferative retinopathy in the newborn rat. Can J Ophthalmol 25, 186–189.Google Scholar