Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. AMD is a multifactorial disease and major risk factors include age, smoking, and chronic activation of the immune system. A recent preclinical study conducted in the Laboratory for Experimental Immunology of the Eye at the University Hospital in Cologne (Germany) revealed a potential new treatment form for AMD patients. Noteably, the results of the study identified that Interferon-?, an immunomodulatory drug that is prescribed to Multiple Sclerosis patients since the 1990s could help to treat retinal inflammatory diseases such as AMD. The study was published in the June 2016 issue of EMBO Molecular Medicine.
AMD occurs in two main clinical forms; the dry form with geographic atrophy and the exudative form. The dry form is characterized by accumulation of cellular debris in the subretinal space while the exudative form typically presents with neovascular processes. Anti-vascular endothelial growth factor (VEGF) medication is presently the gold standard for the treatment of choroidal neovascularization. However, nearly 30% of all AMD patients do not respond to anti-VEGF treatment or lose responsiveness after a few intra-vitreal injections. Moreover, inhibition of angiogenesis does not affect the immunological events and fails to be effective in the dry form of AMD.
The researchers found that mice lacking the interferon-?/? receptor showed a very severe outcome in a laser-induced model of neovascular AMD when compared to control animals. Using specific genetically modified animals the group then identified that one single immune cell population of the retina, termed “microglia” were the main drivers of chronic inflammation and aberrant blood vessel formation. “We did not expect that deficiency of this immune receptor in microglia only would have such dramatic consequences on the complete retina”, says the lead principal investigator Thomas Langmann, professor at the University Hospital of Cologne. Researchers then concluded that restoring of a proper retinal immune system could be achieved by treating the diseased animals with the MS drug interferon-?. The team indeed then found that interferon-? therapy significantly reduced inflammation in the retina that resulted in preserved vision. “Although the immunomodulatory potential of Interferon-? has been studied in an experimental model of AMD, these findings underscore its strategic promise for future therapeutic approaches to controlling chronic inflammation in AMD”, says professor Langmann.
The authors of the publication were associated with the Cologne Laboratory for Experimental Immunology of the Eye (www.expimmeye.uni-koeln.de), the Institute of Neuropathology in Freiburg and the TWINCORE Centre for Experimental and Clinical Infection Research in Hannover, Germany.
Article: Interferon?beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization, Lückoff A, Caramoy A, Scholz R, Prinz M, Kalinke U, Langmann T, EMBO Molecular Medicine, doi: 10.15252/emmm.201505994, published online 3 May 2016.