Table 2.
Lipid Therapies Tested in Age-Related Macular Degeneration Mouse Models
| AMD mouse model | Retinal pathologies observed in model | Pharmacological treatment | Mode of action | Observed effects due to pharmacological treatment | References |
|---|---|---|---|---|---|
| 5-month-old Abca4−/− |
• Delayed dark adaption • Elevated PE in outer segments • Increased A2E in RPE • RPE vacuolization • Increased retinal all-trans-RAL after light exposure • Increased A2E and lipofuscin granules in RPE • Cholesterol and ceramide accumulation in RPE • Increased early endosome number and size • Augmented complement activation |
3 Intraperitoneal injections of desipramine for 4 weeks | Inhibitor of ASMase that prevents ceramide production | • Decreased early endosome volume and number in RPE • Prevented C3a activation and signaling in RPE |
274 |
| 3 Intraperitoneal injections of TO901316 for 4 weeks | LXR agonist | • Decreased early endosome volume and number in RPE | 274 | ||
| Various aged Elovl4mut/− | • Presence of fundus abnormalities • Photoreceptor degeneration • Decreased scotopic ERG a-wave and b-wave • Increased lipofuscin and A2E in RPE • Loss of synapses • Neuroinflammation • Extensive inner retinal remodeling |
Dietary DHA supplementation for various lengths of time | C22:6n-3 fatty acid that has anti-inflammatory, anti-angiogenic and antiapoptotic effects | • Preservation of ERG c-wave in 6-month-treated mutant mice • Preservation of cone function in 12-month-treated mutant mice • Decreased A2E levels in 18-month-treated mutant mice |
280a |
| 10-month-old Apoe−/− | • Increased implicit time for scotopic b-wave • Decreased ERG oscillatory potential amplitudes • Decreased ONL nuclei number • Thicker BrM • Increased retinal cholesterol |
Single intravitreal injection of 4F | APOA1 mimetic with anti-inflammatory and antiatherogenic properties | • Decreased BrM thickness • Decreased esterfied cholesterol deposition in BrM |
290 |
| Intravenous injection of sodium iodate in 6-week-old C57BL/6J | • RPE degeneration • Photoreceptor degeneration • Neuroinflammation |
Dietary HM-10/10 treatment for 3 weeks | APOE/APOJ mimetic possessing antioxidant and anti-inflammatory properties | • Decreased retinal thinning • Prevented photoreceptor degeneration • Reduced cleaved caspase-3 in retina |
291 |
| 6-week-old C57Bl/6J∼30-week HF diet | • Presence of fundus abnormalities • Decrease of scotopic ERG a-wave and b-wave • Accumulation of lipids • RPE vacuolization • Deposition of heterogenous debris below the RPE • Thickened BrM thickness |
Dietary simvastatin treatment for 30 weeks | Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that lowers endogenous cholesterol synthesis | • Decreased prevalance of fundus abnormalities • No accumulation of lipids • Decreased RPE vacuolization • No deposition of heterogenous Debris below the RPE • Decreased BrM thickness |
82 |
a
No beneficial effect was seen in a different study using a different Elovlmut/+ mouse after a dietary DHA supplementation.279
ApoA1, apolipoprotein A-I; APOJ, apolipoprotein J; ASMase, acid sphingomyelinase; DHA, docosahexaenoic acid; PE, phosphatidylethanolamine.