Nicholas A Delamere

Nicholas A Delamere

Department Head, Physiology
Professor, Physiology
Professor, Ophthalmology
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-6425

Research Interest

Nicholas Delamere, Ph.D., studies how ocular pressure (pressure in the eye) is controlled and the way cells transport fluid, and seeks to find methods to regulate the mechanisms involved. His goal is to develop drugs that reduce intraocular pressure, thereby decreasing the severity of glaucoma and damage to the retina. His cataract research also offers a promising model for tissue preservation, which will delay the onset of cataracts. https://delamerelab.medicine.arizona.edu/

Publications

Gao, Y., Galante, M., El-Mallakh, J., Nurnberger, J. I., Delamere, N. A., Lei, Z., El-Mallakh, R. S., & , B. C. (2012). BDNF expression in lymphoblastoid cell lines carrying BDNF SNPs associated with bipolar disorder. Psychiatric genetics, 22(5), 253-5.

To determine whether single nucleotide polymorphisms (SNPs) of the brain-derived neurotrophic factor (BDNF) that have been associated with bipolar illness are associated with physiological dysfunction.

Shahidullah, M., Mandal, A., & Delamere, N. A. (2015). Damage to lens fiber cells causes TRPV4-dependent Src family kinase activation in the epithelium. Experimental eye research, 140, 85-93.

The bulk of the lens consists of tightly packed fiber cells. Because mature lens fibers lack mitochondria and other organelles, lens homeostasis relies on a monolayer of epithelial cells at the anterior surface. The detection of various signaling pathways in lens epithelial cells suggests they respond to stimuli that influence lens function. Focusing on Src Family Kinases (SFKs) and Transient Receptor Potential Vanilloid 4 (TRPV4), we tested whether the epithelium can sense and respond to an event that occurs in fiber mass. The pig lens was subjected to localized freeze-thaw (FT) damage to fibers at posterior pole then the lens was incubated for 1-10 min in Krebs solution at 37 °C. Transient SFK activation in the epithelium was detectable at 1 min. Using a western blot approach, the ion channel TRPV4 was detected in the epithelium but was sparse or absent in fiber cells. Even though TRPV4 expression appears low at the actual site of FT damage to the fibers, SFK activation in the epithelium was suppressed in lenses subjected to FT damage then incubated with the TRPV4 antagonist HC067047 (10 μM). Na,K-ATPase activity was examined because previous studies report changes of Na,K-ATPase activity associated with SFK activation. Na,K-ATPase activity doubled in the epithelium removed from FT-damaged lenses and the response was prevented by HC067047 or the SFK inhibitor PP2 (10 μM). Similar changes were observed in response to fiber damage caused by injection of 5 μl hyperosmotic NaCl or mannitol solution beneath the surface of the posterior pole. The findings point to a TRPV4-dependent mechanism that enables the epithelial cells to detect remote damage in the fiber mass and respond within minutes by activating SFK and increasing Na,K-ATPase activity. Because TRPV4 channels are mechanosensitive, we speculate they may be stimulated by swelling of the lens structure caused by damage to the fibers. Increased Na,K-ATPase activity gives the lens greater capacity to control ion concentrations in the fiber mass and the Na,K-ATPase response may reflect the critical contribution of the epithelium to lens ion homeostasis.

Delamere, N., Shahidullah, M., Tamiya, S., & Delamere, N. A. (2007). Primary culture of porcine nonpigmented ciliary epithelium. Current eye research, 32(6).

Primary culture of nonpigmented ciliary epithelium (NPE) has proved difficult in the past. Here we report development of a method of growing and maintaining primary cultures of NPE from porcine eye. Studies were conducted to confirm that the cultured NPE expressed proteins characteristic of native NPE.

Delamere, N., Shahidullah, M., To, C., Pelis, R. M., & Delamere, N. A. (2009). Studies on bicarbonate transporters and carbonic anhydrase in porcine nonpigmented ciliary epithelium. Investigative ophthalmology & visual science, 50(4).

Bicarbonate transport plays a role in aqueous humor (AH) secretion. The authors examined bicarbonate transport mechanisms and carbonic anhydrase (CA) in porcine nonpigmented ciliary epithelium (NPE).

Borchman, D., Paterson, C. A., & Delamere, N. A. (1989). Ca2+-ATPase activity in the human lens. Current eye research, 8(10), 1049-54.

A membrane-rich preparation of paired human lenses was prepared in such a manner as to preserve ATPase activity. The lipid:protein ratio of these preparations was increased 12-fold with an 85% recovery of total phospholipid. The pattern of stimulation of ATPase activity by a range of calcium concentrations was found to be similar in membrane preparations of epithelium and cortex. The concentration of calcium necessary for half-maximal simulations of ATPase activity was approximately 10(-6) M. Ca2+-ATPase activity is undetectable in the lens nuclear region. A shift in the sensitivity of lens epithelial Ca2+-ATPase activity was observed with increasing age concomitant with a general increase in Ca2+-ATPase activity suggesting age related modifications of the membrane.