Mitotropic Compounds for the Treatment of Age-Related Macular Degeneration

Abstract

Recent histopathologic studies have shown that mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in the pathophysiology of age-related macular degeneration (AMD). We supposed that compounds which improve mitochondrial functions (mitotropic compounds) may show beneficial effects in preventing AMD. Fourteen patients affected by early AMD were treated with a mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs), coenzyme Q₁₀ (CoQ₁₀) and vitamin E, while an equal number of age- and sex-matched patients affected by early AMD were treated with vitamin E only. Recovery time after macular photostress, foveal sensitivity and mean defect in the visual field as well as blood lipid levels were recorded at the beginning and after 3, 6, 9, 12 and 24 months of follow-up. In the treated group, all the visual functions showed slight improvement which was evident after 3 months of treatment and remained nearly stationary by the end of 24 months. The same tests in the control group showed slow worsening. The divergence between treated and control groups became more marked with time, but the difference was not significant at any time of the follow-up. These findings suggest that the blend of ALC, PUFA, CoQ₁₀ and vitamin E may improve retinal functions in early AMD.

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

“…However, the correlation between mitochondrial dysfunction and Bruch's membrane alterations remains to be elucidated through ongoing studies. Clinical studies confirmed that a combination of acetyl-Lcarnitine, ω-3 fatty acids and Coenzyme Q10, after an initial improvement, stabilized several visual functions in early AMD (103). However, further studies are also necessary to reveal how the clinically known risk factors of AMD are different between normal aging and AMD and why alterations of the RPE common to both normal aging and AMD groups occur at a younger age in AMD.…”

Coenzyme Q10 Instilled as Eye Drops on the Cornea Reaches the Retina and Protects Retinal Layers from Apoptosis in a Mouse Model of Kainate-Induced Retinal Damage

“…14 The effects of CoQ10 on the vision and, in particular, on the health of the retina have not been widely investigated. Only a few studies have indicated that oral or intravitreal administration of CoQ10 significantly improves eyesight 18,25,26 and protects RGCs against oxidative stress 27 or high IOP-induced ischemia. 6 The capacity of intraocularly injected CoQ10 to reduce RGC apoptosis in a rat model of ischemia/reperfusion damage has also been reported, 25,28 but the molecular mechanisms have not been revealed.…”

Improvement of Visual Functions and Fundus Alterations in Early Age-Related Macular Degeneration Treated with a Combination of Acetyl-<i>L</i>-Carnitine, n-3 Fatty Acids, and Coenzyme Q10

“…After a careful selection of mitochondriotropic (in short ‘mitotropic’) compounds, i.e. compounds which have particular affinity to mitochondria together with the capability of improving mitochondrial metabolism, a combination of acetyl- L -carnitine (ALC), n-3 fatty acids (n-3 FA), and coenzyme Q10 (CoQ10) was applied to test this hypothesis [20]. …”

“…Several experimental and clinical studies showed that: (a) these compounds from dietary uptake preferentially accumulate in the mitochondria of various organs [33, 34], retina included [35, 36]; (b) this accumulation was associated with functional improvement in the RPE-photoreceptor complex [20], and (c) there is a well-defined synergy between these compounds [37, 38]. Finally, a diet rich in n-3 FA and fish was associated with a lower risk of AMD in epidemiological studies [39, 40].…”