Abstract
Purpose: :
In retinopathy of prematurity, research has mainly focused on angiogenic mediators in hyperoxia/hypoxia and altered nutritional status, with less being known about the role of inflammatory signals. The surfactant proteins A (SP-A) and D (SP-D) are c-type lectins that interact with cytokines and macrophages and are well studied especially in lung disease of prematurity. Here, we present the first study looking at the presence and developmental pattern of SP-A and D in mouse retinal tissue.
Methods: :
C57BL/6J (WT) mice were euthanized, and retinas collected at postnatal day 0 (P0), P2, P5, P7, P14 and 6 weeks of life. SP-A and SP-D localization and levels were evaluated by immunohistochemistry (IHC) and ELISA (expressed as ng/ul + SEM with lung tissue for comparison. Results were analyzed via Student's t-test with a p value of <0.05 significance. The retinas of 6 week old SP-A-/- mice were also visualized via Optical Coherance Tomography (OCT). Observational comparisons were made to WT mice.
Results: :
Retinal SP-A and D expression over the first week of life is similar to the pattern seen in the lung. In the retina, the SP-A level is 6.6 + 0.6 at P0, decreases to 2.8 + 0.4 at P5 (p <0.001), then increases to 6.7 + 1.2 at P17. By IHC, SP-A first appears at the outer segment and the inner neuroblastic layers. Over the next week, it localizes towards retinal blood vessels as well as the developing inner and outer plexiform layers. In the retina, SP-D at P0 is 1.5 + 0.1 and peaks at P5 to 5.4 + 0.7 (p<0.001), then decreasing to 2.1 + 0.2 in adulthood. IHC of SP-D shows a similar pattern to SP-A with localization in the inner plexiform, outer plexiform and outer segment layers in adult mice. OCT and angiography shows that SP-A-/- mice have significantly reduced retinal thickness as compared to WT mice under basal conditions.
Conclusions: :
SP-A and D are both found in the retina in close proximity to the cell layers where Mueller cell bodies and retinal blood vessels are in abundance. Absence of SP-A leads to abnormal retinal development. The mouse pup, at birth, has blood vessel development approximating that of a 24-week fetus. Therefore adequate levels of SP-A and SP-D in the early stages of retinal blood development may be important for maintaining vascular and immune homeostasis in the preterm retina. This is being further evaluated in our lab.
Keywords: retinal neovascularization • retinal development • retinopathy of prematurity