June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
The role of Lipe in lipid metabolism in the retina
Author Affiliations & Notes
  • Seher Yuksel
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Rafael Ufret-Vincenty
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Igor A Butovich
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
    Graduate School of Biomedical Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Footnotes
    Commercial Relationships   Seher Yuksel None; Rafael Ufret-Vincenty None; Igor Butovich None
  • Footnotes
    Support  NEI-R01 EY027349, NEI-R01 EY033181, NIH-Visual Science Core Grant P30 EY030413
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5454. doi:
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      Seher Yuksel, Rafael Ufret-Vincenty, Igor A Butovich; The role of Lipe in lipid metabolism in the retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5454.

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

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Abstract

Purpose : Lipid metabolism is crucial for maintaining retinal homeostasis. Defects in lipid metabolism underlie a variety of severe retinal diseases such as age-related macular degeneration and glaucoma. Lipe encodes for the enzyme hormone-sensitive lipase (HSL) which plays a key role in the hydrolysis of cholesteryl esters (CEs), retinyl esters (REs), triacylglycerols (TAGs), and diacylglycerols (DAGs) in multiple tissues. While hormone sensitive lipase is expressed in the retina, its function and relevance in the retina-RPE-choroid environment is not known. We recently generated Lipe-/- mice; they develop a retinal degeneration. Our objective here is to study the role of Lipe/HSL in retinal lipid metabolism by analyzing the lipid composition in the retina and RPE/choroid of Lipe-/- vs Lipe+/+ mice.

Methods : To prevent the decomposition of retinoids, all procedures and analyses were performed under dim red light. Retina and RPE/Choroid tissue specimens were isolated from Lipe+/+ (n=40 eyes) and Lipe-/- mice (n=40 eyes) using a dissection microscope. The tissues were then combined (8 eyes/sample) into 5 pooled retina samples and 5 pooled RPE/Choroid samples for each genotype. Each pooled sample was placed in a glass vial with chloroform/methanol = 2/1 (vol:vol). Lipids were extracted thrice from all tissue samples. Free cholesterol, CEs, REs, TAGs, and DAGs were analyzed using ultra-high-performance liquid chromatography/high-resolution mass spectrometry. Chemical standards of CEs, REs, and TAGs were used to identify the compounds in retina and RPE/choroid samples.

Results : Untargeted multivariate statistical analysis demonstrated clear differences in the lipid composition between Lipe+/+ and Lipe-/- mouse retina and RPE/choroid. The abundance of CEs, REs, and TAGs was affected. There was a three-fold increase in CEs (e.g. C16:1-CE) in the Lipe-/- mouse retina (p=0.008). Surprisingly, while the amount of retinyl palmitate (RetPalm) in Lipe-/- specimens was three times higher than that in their wild-type littermates (p=0.016), there was only a minimal, statistically insignificant increase in RetPalm in Lipe-/- RPE/choroid (p=0.124).

Conclusions : Lipe deficiency in the retina leads to a decline in the hydrolysis of various ester lipids and the accumulation of TAGs, DAGs and retinyl esters, including retinyl palmitate. These findings help to better understand the pathophysiology of the retinal degeneration we previously reported in Lipe-/- mice.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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