Background: Photoreceptor cell death is a key pathology of retinal
degeneration diseases. To date, the molecular mechanisms for this pathological process
remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play
important roles in different biological events. However, its effect on retinal neuronal cells
Objective: To determine the effect of Jam-c on adult mouse eyes, particularly, on retinal
structure, vasculature and photoreceptor cells, in order to explore potential important
target molecules for ocular diseases.
Methods: Jam-c global knockout mice, endothelial-specific and neuronal-specific Jam-c
conditional knockout mice using Tie2-Cre and Nestin-Cre mice respectively were used in
this study. Mouse eyes were harvested from the different groups and eye size examined.
Cryosections of the eyes were made and stained with Hematoxylin and Eosin (H&E) and
the thicknesses of retinal layers measured. Retinal blood vessels and cone and rod
photoreceptors were analyzed using isolectin B4, peanut agglutinin and rhodopsin as
markers respectively. In vivo Jam-c knockdown in mouse eyes was performed by
intravitreal injection of Jam-c shRNA. Jam-c expression in the retinae was quantified by
Results: Global Jam-c gene deletion in mice resulted in smaller eyes and decreased the
diameters of lens and iris. Jam-c-/- mice display marked thinning of the outer nuclear
layer (ONL), less numbers of photoreceptor cells, and abnormal retinal vasculature.
Importantly, neuronal-specific Jam-c deletion led to similar phenotype, whereas no
obvious defect was observed in endothelial-specific Jam-c knockout mice. Moreover,
Jam-c knockdown by shRNA also decreased ONL thickness and photoreceptor
Conclusion: We found that Jam-c is critically required for the normal size and retinal
structure. Particularly, Jam-c plays important roles in maintaining the normal retinal
thickness, vasculature and photoreceptor numbers. Jam-c thus may therefore have
important roles in various ocular diseases.