Major research findings

Age-related macular degeneration (AMD) is a complex condition that affects the central part of the retina, known as the macula, leading to vision loss. Studies have revealed various factors that contribute to its development. One of the strongest susceptibility genes for AMD is complement factor H (CFH), and its variant (Y402H) has been shown to promote AMD-like pathology development in mice.

Furthermore, studies have highlighted the importance of proper information and support for AMD patients. A study in the UK found that patients often lack adequate information about AMD, leading to difficulties in self-advocating and accessing needed support. 5

Another study suggests that altered photoreceptor metabolism plays a crucial role in AMD progression. Activating the mammalian target of rapamycin complex 1 (mTORC1) in photoreceptors of mice resulted in both early and advanced AMD-like pathologies.

Reasons for the causes

While the exact causes of AMD remain under investigation, several factors have been implicated in its development, suggesting a multifaceted etiology. 4

General causes

Genetic factors

Certain genetic variations, particularly in the complement factor H (CFH) gene, have been strongly associated with increased risk for AMD.

Environmental factors

Diet plays a significant role. High intake of cholesterol and saturated fats has been linked to an elevated risk for AMD. Furthermore, high fat and cholesterol-enriched diets have been shown to accelerate AMD-like pathologies in mice.

Photoreceptor metabolism

Changes in photoreceptor metabolism, specifically an increased expression of certain glycolytic genes, indicating a potential glucose shortage, have been observed in AMD patients.

Complement system

The complement system, a part of the immune system, is implicated in AMD development. Research indicates that abnormal activation of the complement system contributes to the formation of sub-retinal pigment epithelium (RPE) basal deposits, a hallmark of early AMD.

Iron accumulation

Excess iron accumulation in the retina has been associated with AMD. Mouse models have shown that deficiencies in ceruloplasmin and hephaestin, proteins involved in iron homeostasis, lead to retinal iron overload and AMD-like pathologies.

Cellular matrix metabolism

The aryl hydrocarbon receptor (AhR) plays a role in cellular clearance and detoxification. In AMD, AhR activity and protein levels decline with age, and mice lacking AhR develop dry AMD-like pathologies, including disrupted RPE cell tight junctions, accumulation of lipofuscin, and Bruch's membrane thickening.

Countermeasures for the causes

Diet therapy

Maintaining a healthy diet low in cholesterol and saturated fats is recommended. Additionally, diets enriched with DHA have shown promise in alleviating AMD-like pathologies in mice.

Gene therapy

Gene therapy holds potential as a future treatment for AMD.

Drug therapy

Targeting complement factor H, a key player in AMD development, is a promising therapeutic approach. ALKBH5, an enzyme involved in RNA methylation, has been linked to AMD. Inhibition of ALKBH5 using drugs like IOX1 has shown potential in suppressing AMD-related pathologies.

Surgery

While cataract surgery is effective for addressing cataracts, there are concerns that it may increase the risk of worsening AMD. 2 1 3

Comparison between studies

Commonalities between studies

Several studies highlight the complex nature of AMD, emphasizing the contribution of genetic, environmental, and metabolic factors, as well as the involvement of the complement system.

Differences between studies

Different studies focus on specific aspects of AMD pathogenesis. Some delve into genetic mutations, while others explore metabolic changes or the role of iron accumulation in the retina.

Notes on application to real life

AMD is a complex condition with multiple contributing factors. Living a healthy lifestyle, including maintaining a balanced diet, managing weight, and exercising regularly, can help reduce the risk of developing AMD. 4 If you have a family history of AMD, it is essential to discuss your risk factors with your doctor and consider preventive measures.

Limitations of current research

While research has shed light on several factors associated with AMD, there is still much to learn about its pathogenesis and progression. More research is needed to develop targeted therapies and improve our understanding of this complex disease. 4

Future research directions

Future research should focus on developing more effective strategies for preventing and treating AMD. Identifying new therapeutic targets, improving our understanding of disease mechanisms, and finding ways to enhance the quality of life for AMD patients are all essential areas of focus. 4 5

Conclusion

Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults. A combination of genetic, environmental, and metabolic factors contributes to its development. While current treatments have limitations, ongoing research offers hope for more effective preventative strategies and therapies in the future. 4

It is important to adopt healthy lifestyle choices and discuss your risk factors with your doctor. Together, we can contribute to the advancement of research and the development of better treatments for AMD. 4 5