The Hospital Clínic-IDIBAPS has recently published a study underlining the importance of a particular protein, known as factor H (FH), in the predisposition to developing age-related macular degeneration (AMD).

AMD is a chronic, progressive disease that causes irreversible vision loss. It affects the central part of the retina, the macula, which is responsible for central vision and fixation of the gaze, which are needed for activities such as reading, using a computer and driving. It causes blurred central vision and alters the shape and size of the image.

The retina is responsible for transforming the light it receives into a nerve impulse that reaches the brain via the optic nerve. This is how images are perceived. It is the body’s most metabolically active tissue. Because the retina is so complex, the mechanisms that trigger AMD are still being studied. What is known at this point is that persistent inflammation and oxidative stress trigger dysfunction in the retinal pigment epithelium.

In this study, conducted by the Institute of Ophthalmology at Hospital Clínic, the authors discuss the relationship between the structure and function of the family of complement factor H proteins as regulators of inflammation and oxidative stress in the pathophysiology of AMD.

Ageing means the ability to control the balance between pro- and anti-inflammatory signals is reduced, which promotes chronic inflammation and also means an increase in oxidative stress. Factor H, one of the main complement regulators, is able to regulate the inflammatory response, but it also plays a protective role against oxidative stress. However, in patients who are genetically susceptible, with alterations in the factor H family genes CFH and CFHR4, which appears to be unable to control chronic inflammation and damage to the retina.

In patients with the Y402H risk genetic variant, the ability of their factor H to regulate both inflammation and oxidative stress is altered. Meanwhile, in patients with elevated levels of the protein FHR4 due to genetic alterations in the CFHR4 gene in the retina, it competes with factor H and limits its protective capacity.

Combined with the processes associated with ageing, these conditions contribute to the progression of AMD. These findings will allow potential therapies that stimulate the function of altered genes associated with FH function to be developed and tested.

Information documented by: Dr Blanca Molins, Ophthalmology Department at Hospital Clínic de Barcelona, Ocular Inflammation Research Group, IDIBAPS.

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