Granin - Derived Peptides in the Eye

The granins are the acidic proteins of secretory granules and there exist three main members of this family, in particular chromogranin A, chromogranin B and secretogranin II. These proteins are widely distributed throughout neuroendocrine tissues and are stored in large dense core vesicles in neuronal cells. Their functional role is not fully clear but it seems that they might play an important role in the formation of secretory granules. Furthermore, the primary amino acid sequence of the granins features many pairs of basic amino acids and these pairs together with monobasic residues are targets of enzymes which proteolytically process the proteins, in particular the prohormone convertases 1 and 2. Thus the granins might be precursors of smaller fragments and they are indeed cleaved. Processing of chromogranin A leads to the generation of catestatin, vasostatins, pancreastatin, serpinin, WE-14, chromacin, chromofungin, chromostatin, betagranin and parastatin, of chromogranin B to secretolytin and of secretogranin II to secretoneurin, manserin and EM66. These peptides are either biologically highly active and/or of pathophysiological significance and the peptides with the highest degree of biological activity are secretoneurin, catestatin, vasostatins and pancreastatin. For secretoneurin, outstanding effects have been described, in particular it promotes not only both angiogenesis and vasculogenesis but also therapeutic angiogenesis in the hindlimb ischemia and myocardial infarcation model. Others however seem to be functionally inert, especially the chromogranin A-derived peptide GE-25 and the chromogranin B-derived peptide PE-11.