Phenotypes for Sod2 Tg(BEST1-rtTA,tetO-cre)1Yzl MGI:5774839 MGI Mouse

abnormal ocular fundus morphology ( J:230153 )

• by 6 months of age, doxycycline-induced mice show discrete refractive foci in the fundus suggesting localized retinal degeneration

abnormal retina vasculature morphology ( J:230153 )

• doxycycline-induced mice show abnormal retinal blood vessels starting at ~6 months of age

• fluorescein angiography revealed vascular leakage in regions of atrophy, with twisted major blood vessels, vascular beading, and increased branching and dilation of deeper blood vessels

• however, no signs of choroidal neovascularization are observed

retina hemorrhage ( J:230153 )

• at 9 months of age, one doxycycline-induced mouse showed subretinal hemorrhage between the photoreceptors and RPE

abnormal retina pigment epithelium morphology ( J:230153 )

• at 6 weeks of age, neonatally doxycycline-induced mice show extensive oxidative damage to DNA in the RPE, as shown by 8-OHdG staining; most immunoreactivity is in the cytoplasm although some oxidative damage is seen in nuclei

• increased oxidative stress results in accumulation of 4-HNE-modified proteins and superoxide in the RPE

• at 4 months of age, autofluorescence in the RPE is increased by >20-fold, and basal infoldings of the RPE appear disordered

• by 9 months, overall RPE thickness is increased by ~30% relative to that at 1 month of age, with most thickening detected in the superior region (>40%)

abnormal retina pigmentation ( J:230153 )

• by 6 months, doxycycline-induced mice show hypopigmented areas and white spots reflected thinning of the retina

retina pigment epithelium atrophy ( J:230153 )

• doxycycline-induced mice show slowly progressive retina atrophy during aging

• at 6 months or later, large regions of the RPE appear to be absent, with no intact ONL or photoreceptor layer

• by 9 months, disc membranes are more widely spaced, fragmented mitochondria accumulate along the basal surface of the RPE, membrane-filled vacuoles are seen in some areas, and apical microvilli are absent

thin retina outer nuclear layer ( J:230153 )

• in doxycycline-induced mice, the average ONL thickness in the posterior retina is reduced by 15% by 6 months and by 24% by 9 months

abnormal retina photoreceptor layer morphology ( J:230153 )

• at 6 weeks of age, neonatally doxycycline-induced mice show increased accumulation of superoxide in the photoreceptor layer

short photoreceptor inner segment ( J:230153 )

• by 9 months, photoreceptor inner segments are severely shortened in some regions

short photoreceptor outer segment ( J:230153 )

• by 9 months, photoreceptor outer segments are severely shortened in some regions

abnormal retina rod cell outer segment morphology ( J:230153 )

• by 9 months, the length of rod outer segments is increased in many areas of the retina, with gaps between disc membranes

retina photoreceptor degeneration ( J:230153 )

abnormal optic choroid morphology ( J:230153 )

• at 4 months of age, neonatally doxycycline-induced mice show increased autofluorescence in the choroid

• at 6 months of age, the choroid layer shows distension and increased porosity

• by 9 months, the choroid appears less compact and more porous

abnormal Bruch membrane morphology ( J:230153 )

• at 4 months of age, doxycycline-induced mice show enlargement and disorganization of Bruch's membrane

abnormal cone electrophysiology ( J:230153 )

• doxycycline-induced mice show an age-related decline in the photopic b-wave amplitudes which becomes significant by 6 months

abnormal rod electrophysiology ( J:230153 )

• doxycycline-induced mice show an age-related decline in the scotopic a-wave and b-wave amplitudes which becomes significant by 6 months

oxidative stress ( J:230153 )

• at 2 months but not at 1 month of age, mice treated with doxycycline as pups show an 18% increase in nitrotyrosine in RPE/choroid samples, indicating increased oxidative stress

• increased oxidative stress in the RPE is confirmed by 8-OHdG staining and accumulation of 4-HNE-modified proteins and superoxide