Fig. 5. Combination pretreatments improve retinal morphological protection against bright light exposure in Abca4−/−Rdh8−/− mice.
(A) BRM, MTP, or TAM was administered either individually at the indicated subeffective dose (in mg/kg bw) to Abca4−/−Rdh8−/− mice or as a combined pretreatment as indicated, each at its subeffective dose. The mice were then exposed to bright light, and OCT imaging was performed 7 days later. Percentages of mice manifesting complete protection of retinal structures were calculated for each condition. For individual drug treatment, combination treatment with BRM and MTP, and combination treatment with MTP and TAM, n = 12 mice per group. For combination of BRM and TAM, n = 21 per group. For combination of BRM, MTP, and TAM, n = 24 per group. (B) Retinal OCT images of Abca4−/−Rdh8−/− mice either unexposed to bright light or exposed to bright light after pretreatment with DMSO or the indicated drug combinations at the subeffective doses for each. Images were obtained 7 days after light exposure. Asterisk indicates impaired ONL structure. (C) The thickness of the ONL was determined from OCT images at 0.45 mm away from the ONH in the region of the retinas in the direction of the temples from five mice 7 days after light exposure. *P < 0.05, compared to no light; #P < 0.05, compared to DMSO (independent samples t test). (D) SLO was performed to image autofluorescent spots in the retinas of Abca4−/−Rdh8−/− mice unexposed to bright light or exposed to light after the indicated pretreatment. SLO imaging was performed 9 days after light exposure. (E) Gross morphology of retinas was examined after H&E staining of paraffin sections collected from light-exposed Abca4−/−Rdh8−/− mice pretreated as indicated. Retinal tissue was obtained 10 days after light exposure. Asterisk indicates severely diminished ONL. All morphological analyses in (B) to (E) were performed with at least five mice.