Proteoglycan IMPG2 shapes the interphotoreceptor matrix and modulates vision

The extracellular matrix surrounding the photoreceptor neurons, interphotoreceptor matrix (IPM) is comprised of two unique proteoglycans: IP M p roteo g lycan 1 and 2 (IMPG1 and IMPG2). Although the functions of the IPM are not understood, patients with mutations in IMPG1/2 develop visual deficits with subretinal material accumulation. Here, we generated mouse models lacking IMPG1/2 to decipher the role of these proteoglycans and the pathological mechanisms that lead to vision loss. IMPG1 and IMPG2 occupy specific locations in the outer retina, and both proteoglycans are fundamental for the constitution of the IPM system. Mice lacking IMPG2 show abnormal accumulation of IMPG1, and in later stages, develop subretinal lesions and reduced visual function. Interestingly, removal of IMPG1-2 showed normal retinal morphology and function, suggesting that the aberrant localization of IMPG1 causes the alterations observed in IMPG2 KO mice. In conclusion, our results demonstrate the role of IMPG2 in shaping the IPM, shed light on the potential mechanisms leading to subretinal lesions, and show that the secreted proteoglycans depend on the extracellular matrix environment to properly integrate into the matrix.