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Review
. 2020 Nov;245(17):1615-1625.
doi: 10.1177/1535370220926938. Epub 2020 May 21.

Retinoid analogs and polyphenols as potential therapeutics for age-related macular degeneration

Tanu Parmar  1 , Joseph T Ortega  1 , Beata Jastrzebska  1
Affiliations
Review

Retinoid analogs and polyphenols as potential therapeutics for age-related macular degeneration

Tanu Parmar et al. Exp Biol Med (Maywood). 2020 Nov.

Abstract

Age-related macular degeneration (AMD) is a devastating retinal degenerative disease. Epidemiological reports showed an expected increasing prevalence of AMD in the near future. The only one existing FDA-approved pharmacological treatment involves an anti-vascular endothelial growth factor (VEGF) therapy with serious disadvantages. This limitation emphasizes an alarming need to develop new therapeutic approaches to prevent and treat AMD. In this review, we summarize scientific data unraveling the therapeutic potential of the specific retinoid and natural compounds. The experimental results reported by us and other research groups demonstrated that retinoid analogs and compounds with natural product scaffolds could serve as lead compounds for the development of new therapeutic agents with potential to prevent or slow down the pathogenesis of AMD.

Keywords: Degeneration; flavonoids; macula; polyphenols; retina; retinoids.

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Figures

Figure 1.
Figure 1.
Retinoid cycle and synthesis of A2E. Light triggers isomerization of 11-cis-retinal (11-cis-RAL) chromophore to all-trans-retinal (All-trans-RAL). Under normal conditions, all-trans-retinal is reduced to all-trans-retinol (All-trans-ROL) by retinol dehydrogenases 8 and 12 (RDH8 and RDH12, respectively), which then is esterified by lecithin retinol acyltransferase (LRAT) to all-trans-retinyl esters (All-trans-retinyl-RE). These esters can be stored in retinosomes or converted to 11-cis-retinol (11-cis-ROL) by retinal pigment epithelium-specific protein 65 (RPE65) isomerase. 11-cis-Retinol is converted to 11-cis-retinal by retinol dehydrogenase 5 (RDH5), which then can re-associate with opsin forming the visual pigment, rhodopsin. Inefficient reduction of all-trans-retinal to all-trans-retinol results in excess of all-trans-retinal, which can react with phosphatidylethanolamine (PE), resulting in formation of bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E). Accumulated A2E causes an increase of reactive oxygen species (ROS) detrimental to the retinal cells. Overproduction of ROS can be decreased by specific retinoid analogs, dietary carotenoids and polyphenolics, particularly flavonoids. (A color version of this figure is available in the online journal.)
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