Abstract
Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1−/− mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1−/− retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.
Highlights
It is generally accepted that immune responses follow injury and damage to tissues and organs
Genes linked to inflammatory responses, inflammatory diseases and immune cell trafficking were significantly altered in Cngb1−/− retinas at P28 when compared to wt retinas
In Cngb1−/− mice, neuronal cell death does not start before postnatal day 15 (P15) [12]
Summary
It is generally accepted that immune responses follow injury and damage to tissues and organs. Microglia are essential for maintaining a healthy CNS, paradoxically they may undergo phenotypic changes to influence several neurodegenerative diseases and psychiatric disorders including Alzheimer’s disease (AD), Parkinson’s disease, and Rett syndrome [4]. RP is characterized by an initial progressive degeneration of rods and followed by the loss of cones leading to severe visual impairment [8, 10]. It should be noted that the disease severity, rate of disease progression, age of onset and clinical findings may differ significantly among patients based on the fact that RP represents a heterogeneous group of inherited retinal disorders [11]. Subsequent degeneration of cones leads to a gradual loss of the visual field, which initially impairs the periphery and spreads to the macula. The consequences include so-called “tunnel vision” and eventually complete blindness [10]
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