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Deshea L Harris, Arsia Jamali, Alessandro Abbouda, Hamid-Reza Moein, Pedram Hamrah; The Neuropeptide Adrenomedullin as a New Target to Treat Corneal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3521.
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© ARVO (1962-2015); The Authors (2016-present)
Adrenomedullin (ADM) is a small, secreted peptide that can function as a neurotransmitter/modulator and is upregulated in the eye in in the aqueous humor, vitreous humor or plasma in several ocular diseases. Recently we have demonstrated the expression of ADM and its receptors in the cornea. The purpose of this study is to analyze the functional effect of ADM on corneal angiogenesis and lymphangiogensis.
ADM peptide/PBS or ADM/control siRNA were injected subconjunctivally into one eye of BALB/c mice from day -1 to 14 days every other day. At day 0, a subset of the group had one cornea sutured in 3 areas to induce chronic neovascularization whereas the other subset served as controls. At days 3, 7 and 14, the corneas were removed and stained with CD31 for blood vessels and with LYVE-1 for lymphatic vessels. The distance, area, sum length of heme- and lymph-angiogenesis were measured, as well as the diameter of lymphatic vessels.
Exogenous ADM did not have an effect on the heme- or lymph-angiogenesis measured by distance from the limbal vessels, area of the new growth or total sum length of the vessels (P>0.05). However, increased diameter of lymphatic vessels was noted, starting at POD7 in both unsutured (30.53+/-1.79 mm; p=0.001) and sutured corneas (31.56+/-1.22 mm; p<0.001) compared to Sham PBS controls (21.71+/-2.32 mm). Depletion of ADM with siRNA reduces suture-induced heme-angiogenesis (3.03+/-0.63 mm/mm2) as measured by sum length by POD14 compared to control siRNA and (9.83+/-1.1 mm/mm2; p<0.05). The amount of heme-angiogenesis at POD14 with depletion of ADM was even lower than seen at POD3 in the control siRNA samples (7.53+/-1.15 mm/mm2; p=0.01).
This is the first study demonstrating that modulation of adrenomedullin results in diminishment of corneal angiogenesis. ADM may thus serve as a new target for the treatment for corneal angiogenesis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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