July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The Visual Chromophore All-Trans-Retinaldehyde in Retinal Pigment Epithelial Cells: An Alternative Metabolic Pathway
Author Affiliations & Notes
  • Yalin Wu
    Ophthalmology, Xiamen University, Xiamen, Fujian, China
  • Footnotes
    Commercial Relationships   Yalin Wu, None
  • Footnotes
    Support  China National Natural Science Foundation Grants 81570857 and 81700864; the Fundamental Research Funds for the Central Universities grant; Natural Science Foundation of Fujian Province Grants 2017J01148 and 2016J01412; Research Grant for Young and Mid-aged Teachers of Fujian Province JAT160011 and Scientific Research Staring Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of China
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4037. doi:
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    • Get Citation

      Yalin Wu; The Visual Chromophore All-Trans-Retinaldehyde in Retinal Pigment Epithelial Cells: An Alternative Metabolic Pathway
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):4037.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : During the visual (retinoid) cycle, clearance of all-trans-retinaldehyde (atRAL) released from photoactivated rhodopsin involves reisomerization of it back to 11-cis-retinaldehyde, the chromophore binding with opsin to regenerate rhodopsin, in retinal pigment epithelial (RPE) cells. Given that disrupted atRAL clearance will cause severe RPE/photoreceptor dystrophy as well as the production of toxic atRAL condensation byproducts that constitute RPE lipofuscin, free atRAL and RPE lipofuscin are both considered to implicate the etiology of age-related macular degeneration (AMD). As the precursor of bisretinoid constituents of RPE lipofuscin, free atRAL exhibits higher cytotoxicity to RPE cells than bisretinoids A2E and all-trans-retinaldehyde dimer (atRAL-dimer), thereby revealing that the conversion of free atRAL to bisretinoid fluorophores is likely an antidotal process at the start. Only when accumulated beyond a critical level, A2E and atRAL-dimer have the ability to trigger the death of RPE cells. In the present study, an alternative metabolic pathway of the visual chromophore atRAL in RPE cells is elucidated.

Methods : Primary porcine RPE cells laden with atRAL, and irradiated atRAL or atRAL-dimer in RPE cells and cell-free systems were analyzed by high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cellular toxicity was evaluated by MTS assays.

Results : By using primary porcine RPE cells, we found that, after treatment with atRAL, atRAL-dimer readily formed and accumulated in a concentration- and time-dependent manners. Moreover, atRAL-dimer was highly vulnerable to light, and HPLC analysis revealed that irradiation of atRAL-dimer by light produced a series of hydrophilic products that might be relatively easy to be metabolically eliminated. More importantly, exposure of primary porcine RPE cells fed with atRAL-dimer to light showed no cytotoxic effects.

Conclusions : We proposed an alternative metabolic pathway of atRAL in RPE cells: atRAL that evades the visual (retinoid) cycle enters into RPE cells, and undergoes the condensation reaction to generate atRAL-dimer. Light will facilitate the removal of atRAL-dimer without causing RPE cell death. This is the first report on a new concept regarding how atRAL is metabolized in RPE cells.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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