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Anna Salas Torras, Anna Badia, Laura Fontrodona, Barbara Ferreira de Souza, Miguel Angel Zapata, Jose Garcia-Arumi; New insights towards the progression and retinal dysfunction in the laser-induced choroidal neovascularization mouse model.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2628. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Among all the choroidal neovascularization (CNV) animal models available, the laser-induced model has become the most widely accepted and frequently used in the literature. However, the publication of contradictory results about the physiopathology of the model has raised questions concerning the progression of the neovascular areas, which have not been yet completely characterized. Our purpose is to shed more light on the pathological progression and the molecular changes of the LI-CNV mouse model, performing a full in vivo characterization of the lesions progression and the retinal function, together with the study of the immune and pro-angiogenic responses.
Laser was applied in retinas of 10-weeks-old C57BL/6N male mice, burning in 4 or 7 spots per eye at an intensity of 250 mW during 100 ms. Lesions progression was monitored in vivo through optical coherence tomography (OCT) and fluorescent angiography during 14 days and we used focal electroretinography to analyze retinal function. CNV areas were quantified post-mortem 7 and 14 days post-laser. Moreover, we assessed the expression of inflammatory and angiogenic factors in retinal RNA extracts as well as in histological microsections.
Choroidal neovascularization in the injured areas started at day 5 post-laser and correlated with the appearance of sub-retinal fluid exudates in 56% of the lesions, observed by OCT. These neovascular areas reached its maximum growth at day 7, suffering a certain regression on the following days. Retinal function was altered in the areas surrounding the lesions, showing a delay in the implicit time and a reduction in the amplitude of the a-wave. Regarding gene expression evaluation, we reported an overexpression of the pro-inflammatory factors GFAP, MCP-1 and TNF-a in the first 5 days post-laser although, contrary to expectations, pro-angiogenic factors suffered a downregulation after day 3.
The LI-CNV mouse model characterization has confirmed an initial acute inflammatory response followed by a neovascular growth, which reaches its maximum growth by day 7. Moreover, the retinal dysfunction observed in the lesioned areas points towards a predominant affectation of the photoreceptors layer. However, the angiogenic response remains unclear and needs to be further investigated.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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