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Updated: Nov 12, 2025
Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies
Published on: March 12, 2022
Retinal hypoxia and angiogenesis with methamphetamine
Minsup Lee1, Wendy Leskova1, Randa S Eshaq1
1Department of Molecular & Cellular Physiology, Louisiana State University Health Shreveport, Shreveport, LA, 71103, USA.
Abstract:
Central retinal artery occlusion, retinopathy, and retinal neovascularization have been reported in methamphetamine (METH) abusers. In the current study, we investigated whether METH induces retinal neovascularization in a mouse model, and if so, whether the neovascularization is associated with increased hypoxia, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF). Mice were administrated METH by intraperitoneal injection over a 26-day period, or injected with saline as a vehicle control. The number of retinal arterioles and venules were counted using in vivo live imaging following infusion with fluorescein isothiocyanate-dextran. Excised retinas were stained with griffonia simplicifolia lectin I and flat mounted for a measurement of vascularity (length of vessels per tissue area) with AngioTool. Retinal hypoxia was examined by formation of pimonidazole adducts with an anti-pimonidazole antibody, and HIF-1α and VEGFa protein levels in the retina were detected by immunoblot. METH administration increased vascularity (including the number of arterioles) measured on Day 26. Retinal VEGFa protein level was not changed in METH-treated mice on Day 5, but was increased on Day 12 and Day 26. Hypoxia (pimonidazole adduct formation) was increased in retinas of METH-treated mice on Day 12 and Day 26, as were HIF-1α protein expression levels. These results indicate that METH administration induces hypoxia, HIF-1α, VEGFa, and angiogenesis in the retina.
Insights
Methamphetamine (METH) abuse can cause eye damage. This study shows METH induces retinal hypoxia, increasing blood vessel growth (angiogenesis) by activating hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF).
Area of Science:
- Ophthalmology
- Toxicology
- Vascular Biology
Background:
- Methamphetamine (METH) abuse is linked to severe ocular complications, including central retinal artery occlusion and retinopathy.
- Retinal neovascularization, a condition where new blood vessels grow abnormally, has been observed in METH abusers.
Purpose of the Study:
- To investigate if METH administration induces retinal neovascularization in a mouse model.
- To determine if METH-induced neovascularization is associated with increased retinal hypoxia, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF).
Main Methods:
- Mice were administered METH or saline (vehicle control) via intraperitoneal injection over 26 days.
- Retinal vascularity was assessed using in vivo imaging and flat-mounted retinas stained with Griffonia simplicifolia lectin I.
- Retinal hypoxia, HIF-1α, and VEGFa protein levels were measured using pimonidazole adducts and immunoblotting.
Main Results:
- METH administration significantly increased retinal vascularity and the number of arterioles by Day 26.
- Retinal VEGFa protein levels increased on Days 12 and 26 in METH-treated mice.
- Increased retinal hypoxia and HIF-1α protein expression were observed on Days 12 and 26.
Conclusions:
- Methamphetamine administration induces retinal hypoxia, HIF-1α activation, and VEGFa upregulation.
- These molecular changes promote angiogenesis in the retina.
- The findings suggest a mechanism by which METH abuse can lead to sight-threatening ocular neovascularization.
