Lisa Ebihara, MD, PhD
In this section
Dr. Ebihara is studying the biophysical and pharmacological properties of gap junctional channels in the lens of the eye and other tissues. The lens is a transparent, spherical organ whose main purpose is focus light on the retina. It is highly dependent on intercellular communication for volume regulation and metabolic homeostasis. There have been three types of gap junctional proteins (connexins) identified in the mammalian lens: Cx43, Cx46, Cx50. One of the current areas of interest in the field of eye research is to understand how these gap junctional proteins contribute to lens homeostasis and how cataracts arise. It has been recently shown that mutations of lens gap junction proteins are associated with certain forms of inherited congenital cataract. Furthermore, targeted disruption of the genes for either Cx46 or Cx50 result in the development of cataracts in mice.
One of the major aims of Dr. Ebihara's research project are to obtain a more detailed understanding of the biophysical properties of cloned lens gap junctional proteins and to localize the molecular determinants of permeability and gating of the gap junctional channels. Another aim is to examine the functional consequences of mutations of Cx50 and Cx46 found in congenital cataract patients. The techniques employed in these studies include: expression of cloned proteins in the Xenopus oocyte expression system and communication-deficient mammalian cell lines; two-microelectrode-voltage-clamp and patch clamp studies of macroscopic and single channel currents; other molecular biological techniques such as site directed mutagenesis; immunoblot analysis.
- Ebihara L, Tong JJ, Vertel B, White TW and Chen TL. Properties of connexin 46 hemichannels in dissociated lens fiber cells. Invest Ophthalmol Vis Sci 2010.
- Minogue PJ, Tong JJ, Arora A, Russell-Eggitt I, Hunt DM, Moore AT, Ebihara L, Beyer EC and BerthoudVM. A mutant connexin50 with enhanced hemichannel function leads to cell death. Invest Ophthalmol Vis Sci 50: 5837-5845, 2009.
- Arora A, Minogue PJ, Liu X, Addison PK, Russel-Eggitt I, Webster AR, Hunt DM, Ebihara L, Beyer EC,Berthoud VM and Moore AT. A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet 45: 155-160, 2008.