Abstract
Purpose :
Decorin (Dcn), a small leucine-rich proteoglycan (SLRP), is an extracellular matrix (ECM) structural protein in the retina. Dcn is involved in various biological functions, including the modulation of growth factors, cell proliferation, survival, migration, development, and angiogenesis. Previous studies have shown that Dcn is expressed homogenously in embryonic murine retina, but is highly localized to the nerve fiber layer, ganglion cell layer and photoreceptors in matured retina. Furthermore, the synthesis of Dcn is associated with endothelial cord and tube formation, and can interact with multiple ligands and receptors associated with cellular development and angiogenesis. However, Dcn’s functional role in the retina has yet to be investigated. We hypothesize that Dcn plays a functional role in regulating normal retinal development, and that the lack of Dcn will result in abnormal structural and vascular organization.
Methods :
To evaluate how Dcn deficiency can affect retinal microvasculature, postnatal day 30 (P30) wild type (WT), Dcn+/- and Dcn-/- mice retina was imaged using a MicronIV retinal imaging system. Additionally, retinal flat mounts of P30, P42 and P90 mice were stained with Isolectin GS-IB4 for analysis of the different layers of retinal vascular plexuses. Optical coherence tomography (OCT) measurements were recorded to evaluate structural changes in the retina. Retinal function was examined using dark-adapted electroretinogram (ERG) measurements.
Results :
Loss of Dcn results in increased retinal vascular tortuosity with kinks observed around the peripheral retina. The percentage of retinal microvasculature in the peripheral deep vascular plexus is also reduced. Furthermore, OCT measurements revealed increased retinal thickness suggesting changes in retinal structure. The dark-adapted ERG a-wave and b-wave signals were delayed in Dcn deficient mice depicting abnormal retinal function. The b-wave amplitudes of Dcn deficient mice were also significantly reduced, suggesting defects in Muller cell or ON-biopolar cell function.
Conclusions :
Dcn may play a crucial role in the physiological development of the retina and in the maintenance of retinal microvasculature
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.