May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
Exacerbation of Retinal Degeneration Induced by Subretinal Injection of Matrigel in CCL2/MCP–1 Deficient Mice
Author Affiliations & Notes
  • D. Shen
    Laboratory of Immunology, NEI/NIH, Bethesda, MD
  • R. Wen
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • J.S. Tuo
    Laboratory of Immunology, NEI/NIH, Bethesda, MD
  • C.M. Bojanowski
    Laboratory of Immunology, NEI/NIH, Bethesda, MD
  • C.C. Chan
    Laboratory of Immunology, NEI/NIH, Bethesda, MD
  • Footnotes
    Commercial Relationships  D. Shen, None; R. Wen, None; J.S. Tuo, None; C.M. Bojanowski, None; C.C. Chan, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5299. doi:
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      D. Shen, R. Wen, J.S. Tuo, C.M. Bojanowski, C.C. Chan; Exacerbation of Retinal Degeneration Induced by Subretinal Injection of Matrigel in CCL2/MCP–1 Deficient Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5299.

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

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Abstract: : Purpose: In mice, normal function of CC chemokine CCL2 (MCP–1) and its cognate receptor (CCR2) confers some degree of protection against age–related macular degeneration (AMD) in their senescence. Matrigel, a solubilized basement membrane preparation, solidifies after implantation in tissue and is capable of stimulating local angiogenesis. The goal of this study is to compare the retinal degeneration and neovascularization induced by subretinal matrigel injection in CCL2 deficient (KO) and wild type (WT) mice. Methods: Two independent experiments were performed. A total of 11 CCL2 KO and 11 WT mice were subretinally injected with Matrigel (BD Biosciences) in both eyes. Matrigel (75% v/v) was prepared with PBS. The injection was administered under general anesthesia. After exposing the sclera, an incision was made between the limbus and the equator and 0.5 µl matrigel in a Hamilton micro–syringe was introduced into subretinal space. Mice were euthanized at week 4 (4 mice) and 12 (18 mice) post injection. The eyes were harvested, fixed in 10% formalin, embedded in methacrylate and sectioned via the injection site for histological examination. Results: The two experiments had similar results. Pathology demonstrated matrigel located under the RPE at week 4 post injection, either under or above the RPE, between the neuroretina and Bruch’s membrane, which mimics drusen formation. At week 12, there were RPE and photoreceptor degeneration and/or atrophy, RPE migration, various degrees of choroidal neovascularization and mild inflammation (mainly macrophages) surrounding the matrigel in all eyes. More KO mice than WT mice showed neovascularization. Damage to the RPE cells and photoreceptors was observed in both groups. However, overall the damage appears more pronounced in the KO mice, some of which showed a total loss of inner retinal layers. Interestingly, more macrophages were found in WT than in KO mice. Conclusions: Our observations suggest that CCL2 deficiency leads to more severe retinal degeneration in mice injected with matrigel. Impaired macrophage recruitment, resulting in disabled degradation and removal of the subretinal matrigel implant, may cause the accumulation of subretinal or Bruch’s membrane deposits (drusen formation), and promote choroidal neovascularization and photoreceptor atrophy. The model supports the previously proposed protective role of CCL2 in AMD development and may provide a useful platform for studies of retinal degeneration.

Keywords: pathology: experimental • cytokines/chemokines • retinal neovascularization 

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