Abstract
Purpose::
Programmed cell death 1 (PD-1), a member of CD28 family, functions as a negative regulator in immune system, and PD-1 pathway plays a crucial role in down-regulating T cell responses and maintenance peripheral tolerance. PD-1 was previously thought to be exclusively expressed on the activated T cells, B cells and myeloid cells. We recently identified its expression in the retina of adult rodents. The purpose of this study is to identify the PD-1 expressing cells and characterize developmental expression of PD-1.
Methods::
Immunohistochemistry and confocal microscopy was performed to identify PD-1 protein expression in the mouse retina at multiple time points between embryonic day 12 and post natal day 24. Co-localization experiments were performed using antibodies against PD-1, Brn3a, Thy-1, AP2, GFAP, calbindin, and islet to determine the identity of the retinal PD-1-expressing cells. Real-time RT-PCR was also performed to quantify PD-1 mRNA expression in the retina.
Results::
Constitutive expression of PD-1 was observed in the retinal ganglion cell layer of adult retina. Double-labeling immunohistochemistry revealed that 70% of the PD-1 cells were of the retinal ganglion cell lineage and 27% were amacrine cells. The levels of PD-1 expression changed during development. Low levels of PD-1 expression were initially observed at embryonic day 14, and its expression increased during development, reaching a peak at P13 with subsequent decrease to an intermediate expression level at P24.
Conclusions::
PD-1 is expressed in retinal ganglion cells and its expression dynamically changed during retinal development. Expression was first observed in the retina within 2 days of initial retinal ganglion cell appearance. The maximal levels of PD-1 were observed during the critical time of postnatal visual plasticity. This observation raises the possibility of a developmental role for PD-1 in maturation of the ganglion cell layer.
Keywords: retina • retinal development • ganglion cells