AMD and Atherosclerosis: Physiopathogenic Similarities and Possib
Journal of Clinical and Experimental Ophthalmology

Journal of Clinical and Experimental Ophthalmology
Open Access

ISSN: 2155-9570

+44 1223 790975

Editorial - (2012) Volume 3, Issue 6

AMD and Atherosclerosis: Physiopathogenic Similarities and Possible Therapeutics

Rogil J De A Torres*
Pontifícia Universidade Católicado Paraná, Department of Ophthalmology, Curitiba, Brazil
*Corresponding Author: Rogil J De A Torres, Rua Emiliano Perneta 390, Conj 1407, Cep 80240-080, Curitiba, PR, Brazil, Tel: 55-41-32256349 Email:

Chronic inflammatory diseases induced by oxidized Low-Density Lipoprotein (LDL) used to be associated with atherosclerosis. The findings that the hypofunction of the Retinal Pigment Epithelium (RPE) induce accumulation of lipids in the Bruch’s membrane have contributed to the understanding of the physiopathogenesis of the Age-Related Macular Disease (AMD) [1-3]. It has been possible to conclude that the interactions that occur in the formation of the atherosclerotic plaques may also occur in the sclera-choroid-retina complex, that is, the oxidized LDL induces the production of the monocyte chemotactic protein-1 (MCP-1) and increases the expression of the Intercellular Adhesion Molecule-1 (ICAM-1) andVascular Cell Adhesion Molecule- 1 (VCAM-1) by the activated endothelial cells. These molecules attract the circulating monocytes and promote adhesion to the vascular wall. When the recruited monocytes enter the vascular wall intima, they ingest the oxidized LDL and differentiate into macrophages. These cells secrete inflammatory cytokines, enzymes and vascular growth factors and may induce the formation of the Choroidal Neovascularization (CNV).

This hypothesis has been consolidated by different experimental studies. The surgical removal of the CNV has confirmed the increase in the MCP-1 expression by the RPE cells [4], the role of the matrix metalloproteinase in the progressive growth of the CNV and the angiogenic potential role of the macrophages, stimulating the production of the Vascular Endothelial Growth Factor (VEGF) by the RPE [5,6]. In mice with targeted homozygous disruption of the CD18 and ICAM-1 genes, laser-induced neovascular membranes smaller than in normal mice were observed [7]. The same result was obtained in Plasminogen Activator Inhibitor-1 (PAI-1) gene-deficient mice [8]. Moreover, it has been demonstrated that generalized macrophage depression decreases the volume and angiographic leakage of the CNV [9,10].

These experimental evidences have enabled researchers to infer that the measures adopted to prevent the development of atherosclerosis may have the same level of efficiency to prevent the evolution of AMD. In this regard, epidemiological studies have demonstrated that smoking tobacco significantly increases the risk of age-related macular disease [11] and that physical activities [12], a healthy diet [13,14] and the control of serum cholesterol [15,16] are important factors for the prevention of AMD.

Regarding therapeutic procedures, it is possible to assert that the drugs that stimulate the reverse cholesterol transport can also yield similar positive effects on AMD. It is important to point out that macrophages and RPE cells express CD36 [17], Apolipoprotein E (ApoE) [18], scavenger receptor BI (SR-BI) [19], ATP-binding cassette subfamily members A1 (ABCA1) [20] and ApoA1, the major protein constituent of HDL [21]. These components have the potential to remove lipids from RPE and Bruch’s membrane into the choriocapillaries to be metabolized by the liver [21,22]. As in atherosclerosis, the control of the macrophages as well as of their liberation products such as the inflammatory cytokines, enzymes and growth factors may appear to have the same beneficial effects on the control of AMD.

Hence, nowadays, when we discuss oxidized LDL-induced chronic inflammatory diseases, AMD must also be considered.


  1. Hogan MJ (1972) Role of the retinal pigment epithelium in macular disease. Trans Am Acad Ophthalmol Otolaryngol 76: 64-80.
  2. Hageman GS, Luthert PJ, Victor Chong N H, Johnson LV, Anderson DH, et al. (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. ProgRetin Eye Res 20: 705-732.
  3. Grossniklaus HE, Ling JX, Wallace TM, Dithmar S, Lawson DH, et al. (2002) Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis 8: 119-126.
  4. B Steen, S Sejersen, L Berglin, S Seregard, A Kvanta (1998) Matrix metalloproteinases and metalloproteinases inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci 39: 2194-2200.
  5. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, et al. (1999) The PotencialAngiogenic Role of Macrophages in the Formation of Choroidal Neovascular Membranes. Invest Ophthalmol Vis Sci40: 1891-1898.
  6. Sakurai E, Taguchi H, Anand A, Ambati BK, Gragoudas ES, et al. (2003) Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 2743-2749.
  7. Lambert V, Munaut C, Noël A, Frankenne F, Bajou K, et al. (2001) Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization. FASEB J 15:1021-1027.
  8. Espinosa-Heidmann DG, Suner IJ, Hernandez EP, Monroy D, Csaky KG, et al (2003)Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci44: 3586-3592.
  9. Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3578-3585.
  10. Tan JS, Mitchell P, Smith W, Wang JJ (2007) Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 114: 1143-1150.
  11. Seddon JM, Cote J, Davis N, Rosner B (2003) Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio. Arch Ophthalmol 121: 785-792.
  12. van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, et al. (2005) Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 294: 3101-3107.
  13. Chiu CJ, Hubbard LD, Armstrong J, Rogers G, Jacques PF, et al. (2006) Dietary glycemic index and carbohydrate in relation to early age-related macular degeneration. Am J ClinNutr 83: 880-886.
  14. Dashti N, McGwin G, Owsley C, Curcio CA (2006) Plasma apolipoproteins and risk for age related maculopathy. Br J Ophthalmol. 90: 1028-1033.
  15. McCarty CA, Mukesh BN, Guymer RH, Baird PN, Taylor HR (2001) Cholesterol-lowering medications reduce the risk of age-related maculopathy progression. Med J Aust 175: 340.
  16. Finnemann SC, Silverstein RL (2001) Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J Exp Med 194: 1289-1298.
  17. Ishida BY, Bailey KR, Duncan KG, Chalkley RJ, Burlingame AL, et al. (2004) Kane JP, Schwartz DM. Regulated expression of apolipoprotein E by human retinal pigment epithelial cells. J Lipid Res 45: 263-271.
  18. Duncan KG, Bailey KR, Kane JP, Schwartz DM (2002) Human retinal pigment epithelial cells express scavenger receptors BI and BII. BiochemBiophys Res Commun 292: 1017-1022.
  19. Duncan KG, Hosseini K, Bailey KR, Yang H, Lowe RJ (2009) Expression of reverse cholesterol transport proteins ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and retinal pigment epithelium. Br J Ophthalmol 93: 1116-1120.
  20. Ishida BY, Duncan KG, Bailey KR, Kane JP, Schwartz DM (2006) High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture. Br J Ophthalmol 90: 616-620.
  21. Rader DJ (2003) Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol 92: 42J-49J.
Citation: de A Torres RJ (2012) AMD and Atherosclerosis: Physiopathogenic Similarities and Possible Therapeutics. J Clin Exp Ophthalmol 3:e111.

Copyright: © 2012 de A Torres RJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.