HMOX1 and obesity due to melanocortin 4 receptor deficiency: It has been shown that although Shh is upregulated in retinas exposed to ocular hypertension, and both exogenous and endogenous Shh have neuroprotective effects on damaged retinal ganglion cells, they did not affect intraocular pressure [12] Also in a model of obesity-associated hypertension, targeting adipocytes in mice fed a high-fat diet with human heme oxygenase-1 gene decreased adiposity and hypertension that was accompanied with increased Shh expression in adipocytes [13].