Immune response in retinal degenerative diseases - Time to rethink?

Retinal degeneration comprises a group of diseases whereby either the retinal neurons or the neurovascular unit degenerates leading to the loss of visual function. Although the initial cause varies in different conditions, inflammation is known to play an important role in disease pathogenesis. Recent advances in molecular and cell biology and systems biology have yielded unexpected findings, including the heterogeneity of immune cells in the degenerative retina, bidirectional neuron-microglia cross talk, and links to the gut microbiome. Here we discuss the immune response in retinal degenerative conditions, taking into account both regional (retinal) and systemic factors. We propose to classify retinal degeneration into dry and wet forms based on whether the blood-retinal barrier (BRB) is breached and fluid is accumulated in retinal parenchyma. The dry form has a relatively intact BRB and is characterised by progressive retinal thinning. Immune response to degenerative insults is dominated by the retinal defence system, which remains to be regulated by neurons. In contrast, the wet form has retinal oedema due to BRB damaged. Inflammation is executed by infiltrating immune cells as well as the retinal defence system. The gut microbiome will have easy access to the retina in wet retinal degeneration and may affect significantly retinal immune response.