Arguing a Role for TIMP3 in Age-Related Macular Degeneration
Researchers here find a role for TIMP3 overexpression in the progression of macular degeneration, an age-related deterioration of the retina that causes blindness. Interestingly, TIMP3 was previously shown to contribute to the age-related decline in stem cell function, and its removal appears beneficial in aged mice. The research noted here was conducted in vitro, using stem cells as a rough model of macular degeneration, which may explain why TIMP3 appeared as a relevant mechanism. It pays not to be too excited by research of this nature until positive results are produced in animal models, however.
The study utilized human stem cells to model age-related macular degeneration (AMD), overcoming the limitations of previous research using animal models. By examining genes associated with both AMD and rarer inherited forms of blindness called macular dystrophies, the researchers identified a key protein involved in the early stages of the disease. The retinal pigment epithelium (RPE), a layer of cells at the back of the eye, plays a crucial role in AMD. Over time, deposits of lipids and proteins, known as drusen, accumulate in the RPE. These deposits are often an early indicator of AMD.
The researchers discovered that a protein called tissue inhibitor of metalloproteinases 3 (TIMP3) is overproduced in AMD. TIMP3 inhibits the activity of enzymes called matrix metalloproteinases (MMPs), which are essential for eye health. Impaired MMP activity leads to increase in another enzyme which promotes inflammation and the formation of drusen. By using a small molecule inhibitor to block the activity of the enzyme associated with inflammation, the researchers were able to reduce drusen formation in their model, suggesting that targeting this pathway could be a promising strategy for preventing AMD.