https://orcid.org/0000-0002-2822-8133
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Abstract
Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era. Lutein and Zeaxanthin are oxygenated carotenoids with proven roles in augmentation of ocular health largely by virtue of their antioxidant properties and protective effects against photobleaching of retinal pigments, age-linked macular degeneration, cataract, and retinitis pigmentosa. These molecules are characterized by their characteristic yellow-orange colored pigmentation and are found in significant amounts in vegetables such as corn, spinach, broccoli, carrots as well as fish and eggs. Unique structural signatures including tetraterpenoid skeleton with extensive conjugation and the presence of hydroxyl groups at the end rings have made these molecules evolutionarily adapted to localize in the membrane of the photoreceptor cells and prevent their free radical induced peroxidation. Apart from the benefits imparted to ocular health, lutein and zeaxanthin are also known to improve cognitive function, cardiovascular physiology, and arrest the development of malignancy. Although abundant in many natural sources, bioavailability of these compounds is low owing to their long aliphatic backbones. Under the circumstances, there has been a concerted effort to develop vegetable oil-based carriers such as lipid nano-emulsions for therapeutic administration of carotenoids. This review presents a comprehensive update of the therapeutic potential of the carotenoids along with the challenges in achieving an optimized delivery tool for maximizing their effectiveness inside the body.
KEY TEACHING POINTS
Lutein and zeaxanthin are the two most abundant natural xanthophylls (oxygenated carotenoids) with a linear C40 tetraterpene/isoprenoid lycopene-based backbone.
Presence of extensive conjugation (more than 10 double bonds) enable these molecules to act as accessory light harvesting pigments apart from chlorophyll.
More importantly, the xanthophylls prevent photobleaching of the pigments and proteins in the Light Harvesting Complex (LHC) by sequestering the excess unutilized blue light and preventing triplet chlorophyll associated formation of Reactive Oxygen Species.
In human eye, lutein, zeaxanthin along with mesozeaxanthin constitute the three macular pigments forming the so called “yellow spot” of the macula and are implicated in maintaining the redox balance, homeostasis and normal physiology of the eyes.
However, unlike plants, xanthophylls must be acquired from dietary sources such as colored leafy vegetables and egg yolk.
Increase in the number of eye diseases in the aging population coupled with insufficient bioavailability of xanthophylls has mandated the industrial production of supplements enriched in xanthophylls.
The bioavailability and delivery of xanthophylls can be significantly enhanced by suspension in a blend of extra-virgin olive oil and other vegetable oils.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Figure 1. Structure of the three macular pigments and the chemical basis of their photoprotective action. (A) Lutein is chemically a 3 R,3′R,6′R-β,ε-carotene-3,3′-diol derived from alpha carotene whereas the precursor of zeaxanthin (3 R,3′R-β,β-carotene-3,3′-diol) is beta carotene. Zeaxanthin has a double bond between 4th and 5th carbon atoms instead of 5th and 6th which extends conjugation and makes zeaxanthin a more efficient chromophore. Mesozeaxanthin is synthesized by isomerization of lutein inside macula only and is an equally efficient photoprotective chromophore as zeaxanthin. The three macular pigments together ensure elimination of harmful blue light, sequestration of singlet oxygen and minimization of chromatic aberration. (B) Mechanism of bio-protective action of lutein and zeaxanthin: Although the UV light is filtered from entering the eye by the eye carotenoid 3 hydroxykynurenine (A), it can still give rise to Reactive Oxygen Species (ROS) both from the photooxidation events as well as the intrinsic metabolic activities going on inside the eye (B) causing elicitation of inflammatory response. The retina containing the photosensitive rod cells and cone cells as well as the eye lens are susceptible to the effect of free radicals and resultant inflammatory response causing irreversible partial or complete blindness over a period of time (C) The macular carotenoids, lutein and zeaxanthin can align themselves in the membrane of the rod cells due to their partial amphiphilic character, presence of several conjugated double bonds in these molecules help to quench the free radicals and thus protect the rod and cone cells membranes from peroxidation and other injuries (D).
Figure 2. Biodelivery of macular carotenoids: Due to the presence of long chain aliphatics, lutein and zeaxanthin pigments must be packaged into a compatible vegetable oil-based liposome for ensuring optimal delivery and bioavailability. After being transported through the blood vessels, these liposomes are taken up by intestinal cells by inclusion into chylomicrons and subsequent delivery into the lymphatics. A new commercially viable formulation of these pigments made from marigold petals uses a mixture of extra virgin olive oil and canola oil and quercettagetin (antioxidant) to achieve a shelf life of 36 months at 25 °C.
