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Updated: Mar 29, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Deletion of SPARC Enhances Retinal Vaso-Obliteration in Mouse Model of Oxygen-Induced Retinopathy
Doaa Sobeih1, Khaled A Hussein1, Neveen Said2
1Oral Biology/Anatomy, College of Dental Medicine, Georgia Regents University (GRU), Augusta, GA, USA ; James & Jean Culver Vision Discovery Institute, GRU, USA ; Ophthalmology, Medical College of Georgia (MCG), GRU, USA.
Background:
Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein which is implicated in regulation of angiogenesis.
Purpose:
To characterize the changes in SPARC expression and effect of its deletion in a mouse model Oxygen Induced Retinopathy (OIR).
Materials And Methods:
Wild type (wt) and SPARC-deficient mice were subjected to high oxygen (75%) for 5 days (p7-p12) before room air for additional 5 days (p12-p17). Retinas from both groups were flat mounted and retinal vessels were labeled with Isolectin-B4. Areas of Retinal Neovascularization (RNV) and vaso-obliteration were measured by Image-J and normalized to total retinal areas. SPARC expression was analyzed in both groups at p14 and p17 in retinal homogenates and sections by Western Blotting (WB) and immunofluorescence respectively. Human Retinal Endothelial Cells (HRECs) were exposed to hypoxia (1% O2) for 6 hours then SPARC was measured in cell lysate and condition medium by WB and ELISA. Moreover, HRECs were treated with VEGF or SPARC to study their mutual regulatory effect.
Results:
SPARC-deficient mice demonstrated significant increase in the vaso-obliteration (p=0.03) and modest increase in RNV compared to the wt control. Retinal levels of SPARC was significantly decreased during OIR at p14 (p=0.01) and partially restored to normal level by p17. Moreover, hypoxia significantly reduced SPARC expression and secretion in HRECs (p=0.001). We noticed a mutual positive regulatory feedback between SPARC and VEGF.
Conclusion:
SPARC deletion enhances ischemic retinopathy, thus modulation of SPARC expression could be a novel therapeutic approach to prevent pathological RNV.
Insights
Secreted Protein Acidic and Rich in Cysteine (SPARC) deletion worsens oxygen-induced retinopathy in mice. Modulating SPARC may offer a new therapy for preventing pathological retinal neovascularization.
Area of Science:
- Ophthalmology
- Vascular Biology
- Cell Biology
Background:
- Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein involved in regulating angiogenesis.
- Oxygen-induced retinopathy (OIR) is a significant cause of vision loss.
Purpose of the Study:
- To investigate the role of SPARC in OIR by examining SPARC expression and the effects of its genetic deletion.
- To characterize SPARC's impact on retinal neovascularization (RNV) and vaso-obliteration.
Main Methods:
- SPARC-deficient and wild-type mice were subjected to an OIR model.
- Retinal neovascularization and vaso-obliteration were quantified.
- SPARC expression was analyzed in retinal tissues and human retinal endothelial cells (HRECs) under hypoxic conditions.
- The interaction between SPARC and VEGF was studied in HRECs.
Main Results:
- SPARC deficiency led to increased vaso-obliteration and RNV in the OIR model.
- SPARC levels decreased during OIR and partially recovered later.
- Hypoxia reduced SPARC expression and secretion in HRECs.
- A positive feedback loop between SPARC and VEGF was observed.
Conclusions:
- SPARC deletion exacerbates ischemic retinopathy.
- Targeting SPARC expression presents a potential therapeutic strategy for preventing pathological RNV in OIR.
