Geographic Atrophy Drug Discovery Service

As a leading company in biotechnology, Creative Biolabs provides efficient and stable one-stop geographic atrophy solutions through our stable and reproducible experimental data.

Background of Geographic Atrophy

Geographic atrophy (GA) is an advanced stage of age-related macular degeneration. When the macula expands to a certain size, it eventually leads to the degeneration of macular photoreceptors, retinal pigment epithelial cells, and choriocapillaris, eventually causing irreversible vision loss. During the onset of GA, if the macula is preserved, the effect on vision will be weak, but if the GA extends through the fovea, it may cause serious vision problems.

Pathology of GA

The pathogenesis of GA is multifactorial, but genetic, histological, and preclinical studies agree that dysregulation of the complement cascade is a key factor in GA pathology. The metabolic demands of photoreceptors in life, photo-oxidation and environmental stress gradually accumulate with time and age, resulting in the gradual appearance and precipitation of extracellular drusen and intracellular lipofuscin. These precipitates and other products of oxidative stress ultimately trigger inflammation through pathways such as the complement cascade and the NLRP3 inflammasome.

Fig 1. Pathophysiology of geographic atrophy. (Boyer, 2017)

The complement cascade is activated through the classical, alternative or lectin pathways, three cascades polymerize to generate complement C3 convertase, which cleaves C3 to generate complement C5 convertase, and finally cleaves C5 into two components, C5a and C5b. Mistakes in this process can lead to the loss of key end-effector components and cell death. The NLRP3 inflammasome is a multi-protein scaffold mainly composed of NLRP3, the adaptor molecule ASC and caspase-1, which has also been proposed as a possible pathogenic factor for the presence of GA.

Therapeutic Approaches for GA

Diagnosis of GA is mainly performed by non-invasive tools such as fundus autofluorescence, structured optical coherence tomography, and OCT angiography. GA itself does not yet have any approved treatments, but lifestyle improvements and specific nutritional supplements are used to prevent and slow the progression of the disease. In the meantime, several drugs and therapeutic approaches are being evaluated with promising results.

• Neuroprotective

Neuroprotective drugs are believed to play an important role in the process of GA. Currently, brimonidine and ciliary neurotrophic factor-501 (CNFT) have shown a certain protective effect on retinal cells in animal models.

• Anti-inflammatory drugs

Chronic inflammation and the complement cascade play an important role in the development of GA, and corticosteroid drugs and complement inhibitor drugs are currently being investigated for GA.

Fig 2. Drug design targets the complement cascade. (Boyer, 2017)

• Vasodilator

Vasodilators can improve choroidal blood circulation and slow the progression of GA.

• Cell transplantation

Another promising research in the treatment of GA is stem cell therapy. Stem cell transplantation may repair and regenerate photoreceptors, but practical applications still require long-term clinical experiments and a multidisciplinary approach.

Our Services

• In Vitro Services
• In Vivo Services
• Ex Vivo Services
• Discovery Services
• Development Services
• Mechanism of Action (MoA) Studies

Creative Biolabs has been working in the field of biology areas for more than a decade, and our scientists are fully confident of completing the most challenging projects. We now offer one-stop solutions for GA therapeutic approaches to our clients all over the world. No matter what stage your research are in, we can propose a feasible and reliable solution for you. So please do not hesitate to contact us and discuss your needs.

Reference

1. Boyer, D.S.; et al. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina. 2017, 37: 819-835.