Abstract
The functioning of the human eye in the extreme range of light intensity requires a combination of the high sensitivity of photoreceptors with their photostability. Here, we identify a regulatory mechanism based on dynamic modulation of light absorption by xanthophylls in the retina, realized by reorientation of pigment molecules induced by trans–cis photoisomerization. We explore this photochemically switchable system using chromatographic analysis coupled with microimaging based on fluorescence lifetime and Raman scattering, showing it at work in both isolated human retina and model lipid membranes. The molecular mechanism underlying xanthophyll reorientation is explained in terms of hydrophobic mismatch using molecular dynamics simulations. Overall, we show that xanthophylls in the human retina act as “molecular blinds”, opening and closing on a submillisecond timescale to dynamically control the intensity of light reaching the photoreceptors, thus enabling vision at a very low light intensity and protecting the retina from photodegradation when suddenly exposed to strong light.
Highlights
The xanthophylls lutein (Lut), zeaxanthin (Zea), and mesozeaxanthin (m-Zea) are indispensable constituents of the human retina, protecting photoreceptors against photodamage.[1−3] The xanthophylls in the retina are present mostly in the yellow spot, the cone-rich region responsible for high-acuity central vision.[4]
A low level of the macular xanthophylls correlates with a high risk of age-related macular degeneration (AMD) that leads to irreversible vision loss.[5]
Gaussian was used to perform blue in the color-coded Fluorescence Lifetime Imaging Microscopy (FLIM) images represent xanthophyllrich regions characterized by relatively short fluorescence lifetimes.[20]. This assignment is confirmed by the fluorescence spectra recorded from single axons (Figure 2b), typical for the emission of polyenes with the conjugated double-bond system N = 10 and 11.21 To our surprise, we found that increasing probing light intensities yielded drastically different relative amplitudes of time-dependent density functional theory (TD-DFT) calcu- the short-lifetime component representing xanthophylls lations on each structure in two variants, either (a) using the (Figures 2a,c and S1d)
Summary
The xanthophylls lutein (Lut), zeaxanthin (Zea), and mesozeaxanthin (m-Zea) (see Figure 1 for chemical structures) are indispensable constituents of the human retina, protecting photoreceptors against photodamage.[1−3] The xanthophylls in the retina are present mostly in the yellow spot (macula lutea), the cone-rich region responsible for high-acuity central vision.[4] A low level of the macular xanthophylls correlates with a high risk of age-related macular degeneration (AMD) that leads to irreversible vision loss.[5] Photooxidative damage of biomolecules in the retina is recognized as one of the leading causes of AMD.[5] Despite a general agreement regarding the protective activity of the macular xanthophylls against photodegradation,[2,6−8] the specific molecular mechanisms involved in this activity in the retina are still not fully understood. We present the operation of a number of molecular mechanisms that can be considered a manifestation of unknown regulatory activity in the human retina. The physiological role of this postulated regulatory mechanism is to dynamically adjust the number of photons reaching the photoreceptors in response to changes in light intensity
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