• levels of lipofuscin and its associated metabolites are 20-fold higher than in controls in the retinal pigment epithelium of mice supplemented with vitamin A

• A2E fluorescent product (from condensation of all-trans-retinal) is detected at much higher levels than in wild-type or Rdh12-deficient mice

• mice supplemented with vitamin A accumulate more higher levels of all-trans retinoic acid in both the liver and eyes

• levels of lipofuscin and its associated metabolites are 20-fold higher than in controls in the retinal pigment epithelium of mice supplemented with vitamin A

• the outer segment is approximately 40% degenerated with OS shortening by 11 months of age

• levels of lipofuscin and its associated metabolites are higher than in controls in the retinal pigment epithelium of mice, especially when diet is supplemented with vitamin A

• the fractional area of lipofuscin granules in the RPE is 0.11 and reaches 0.14 when supplemented with vitamin A as compared to 0.053 in albino controls fed a control diet

• the outer nuclear layer of 11-month old albinos contains 6 to 7 rows compared to 10 to 11 rows for controls

• levels of lipofuscin and its associated metabolites are higher than in controls in the retinal pigment epithelium of mice, especially when diet is supplemented with vitamin A

• the fractional area of lipofuscin granules in the RPE is 0.11 and reaches 0.14 when supplemented with vitamin A as compared to 0.053 in albino controls fed a control diet

• the outer segment is approximately 40% degenerated with OS shortening by 11 months of age

• mutants exhibit a 1.6-fold increase in phosphatidyletanolamine in the outer segments of retinal pigment epithelium

• mutants exhibit the presence of protonated and absence of nonprotonated N-retinylidene-phosphatidylethanolamine in outer segments

• mutants show a 35% mean reduction in a-wave amplitude up to 1 year of age, suggesting a slow photoreceptor degeneration

• 16 and 20 week old mutants exhibit lipofuscin accumulation in the retinal pigment epithelium

• 44 week old eyes show accumulation of dense bodies within retinal pigment epithelium cells, including large oval structures of high electron density

• Bruch's membrane between the retinal pigment epithelium and choroid is thickened

• mutants exhibit a transient accumulation of all-trans- retinaldehyde and transient depletion of all-trans-retinol and all-trans-retinyl esters following photobleach

• mutants exhibit a 1.6-fold increase in phosphatidyletanolamine in the outer segments of retinal pigment epithelium

• mutants exhibit the presence of protonated and absence of nonprotonated N-retinylidene-phosphatidylethanolamine in outer segments

• mutants show a 35% mean reduction in a-wave amplitude up to 1 year of age, suggesting a slow photoreceptor degeneration

• 16 and 20 week old mutants exhibit lipofuscin accumulation in the retinal pigment epithelium

• 44 week old eyes show accumulation of dense bodies within retinal pigment epithelium cells, including large oval structures of high electron density

• Choroidal Neovascularization (CNV) in 22.2% (2/9) of the eyes

• no Choroidal Neovascularization (CNV) in the eyes of sirolimus-treated mice

• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively

• reduced number of cone photoreceptors

• retinylamine treatment largely preserve cone photoreceptors

• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine

• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• disrupted inner membrane cristae in RPE cells at 5 months of age

• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age

• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• di-retinoidpyridinium-ethanolamine (A2E) accumulation

• retinylamine significantly decreased A2E accumulation

• complement deposition on Bruch's membrane

• reduced complement deposition in antioxidant, 9cRAc, and sirolimus-treated mice

• no complement deposition in retinylamine-treated mice

• severely reduced outer nuclear layer

• early retinal degeneration is detected by 6 to 8 weeks of age in mice kept in dim room light (3-5 lux)

• reduced lengths of photoreceptor outer segments (less than 5 micrometers)

• antioxidant, 9cRAc, retinylamine and sirolimus treatment have efficacy in preventing retinal degeneration

• hyaline-like deposits in the rosette structure in 3- to 5-month-old mutant mice

• reduced a- and b-wave amplitudes

• both a- and b-wave amplitudes are maintained significantly better in antioxidant, 9cRAc, retinylamine and sirolimus-treated mice

• reduced Flicker ERG responses

• responses of some antioxidant- and 9cRAc-treated mice are significantly retained after both 20- and 30-Hz stimuli

• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively

• reduced number of cone photoreceptors

• retinylamine treatment largely preserve cone photoreceptors

• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine

• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• disrupted inner membrane cristae in RPE cells at 5 months of age

• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age

• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• di-retinoidpyridinium-ethanolamine (A2E) accumulation

• retinylamine significantly decreased A2E accumulation

• Choroidal Neovascularization (CNV) in 22.2% (2/9) of the eyes

• no Choroidal Neovascularization (CNV) in the eyes of sirolimus-treated mice