M. Joseph Costello, Ph.D.

Costello
mjc@med.unc.edu

Lab Personnel

Professor

  • B.S.E., George Washington University, 1964
  • Ph.D., Duke University, 1971
  • Postdoc, Duke University, 1971-74
  • Postdoc, The Centre de Génétique Moléculaire, 1974-75

Funding Sources

  • National Institutes of Health

Research Interests

The main research project is to determine the role of intercellular junctions in normal development, cell aging and cataract formation in human and animal lenses. The lens is an avascular epithelioid tissue contained within a capsule. Unlike other stratified epithelia, the lens does not slough off cells. Thus, the adult lens contains a gradient of aged fiber cells with the most recently formed cells on the lens surface and the oldest cells in the lens center. Because the lens is avascular, fiber cells communicate through extensive gap junctions in order to exchange small molecules, such as water, nutrients, second messengers and toxins. The lens has the highest density of gap junctions of any mammalian tissue and, in some regions, gap junctions can cover up to 50% of the cell surface. Our major interest is in the age-related changes in gap junctions and their role in cell functions in the older cells in the lens interior. Our current goal is to obtain more detailed data on gap junction function using laser confocal light microscopy combined with measurements of intracellular dye transfer.

Costello Image

Another critical feature of lens fiber cells is their close adhesion. A junction specialized for keeping fiber cells in close apposition is composed of large crystalline arrays of a membrane water channel, aquaporin, that is thought to regulate the volume of the extracellular space essential for maintaining transparency. The close contact also helps the fiber cells to behave as a unified mass during accommodation. We have shown that the aquaporin junctions change dramatically with age causing relatively flat cells in the outer layers to become highly corrugated as the fiber cells age and become more internalized. Our results also indicate that the aquaporin junctions are involved in formation of certain kinds of cataracts. A specific segment of the aquaporin junction breaks down, exposing the cytoplasm to the extracellular space and initiating a series of cellular changes that lead to dense central opacities. Our goals are to understand the molecular events involved in membrane breakdown and to suggest strategies for impeding the progression of age-related changes.

Selected Publications

 

  • Gilliland KO, Johnson S, Metlapally S, Costello MJ, Ramamurthy B, Krishna PV, Balasubramanian D. Mie light scattering calculations for multilamellar bodies in Indian age-related nuclear cataracts. Mol. Vision 14, 572-82, 2008.
  • Costello MJ, Gilliland KO, Metlapally S, Ramamurthy B, Krishna PV, Balasubramanian D. Ultrastructural analysis of damage to nuclear fiber cell membranes in advanced cataracts from India. Exp. Eye Res. 87, 147-158, 2008.
  • Metlapally S, Costello MJ, Gilliland KO, Ramamurthy B, Krishna PV, Balasubramanian D, Johnsen S. Analysis of nuclear lens fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye-Bueche theory. Exp. Eye Res. 86, 434-444, 2008.
  • Costello MJ, Johnsen S, Metlapally M, Gilliland KO, Frame L, Balasubramanian D. Multilamellar spherical particles as potential sources of excessive light scattering in human age-related nuclear cataracts. Exp. Eye Res. 91:881-889, 2010.
  • Costello MJ, Burette A, Weber M, Metlapally S, Gilliland KO, Fowler WC, Mohamed A, Johnsen S. Electron Tomography of Fiber Cell Cytoplasm and Dense Cores of Multilamellar Bodies from Human Age-Related Nuclear Cataracts. Exp. Eye Res. 101:72-81, 2012.
  • Taylor VL, Al-Ghoul KJ, Lane CW, Davis VA, Kuszak JR and Costello MJ. Morphology of the normal human lens. Invest Ophthalmol Vis Sci 37: 1396-1410, 1996.
  • Al-Ghoul KJ, Lane CW, Taylor VL, Fowler WC and Costello MJ. Distribution and type of morphological damage in human nuclear age-related cataracts. Exp Eye Res 62: 237-251, 1996.
  • Taylor VL and Costello MJ. Fourier analysis of textural variations in human normal and cataractous lens nuclear fiber cell cytoplasm. Exp Eye Res. 69, 163-174, 1999.
  • Al-Ghoul KJ, Nordgren R, Kuszak AJ, Freel, CD, Costello MJ. And Kuszak JR. Structural evidence of human nuclear fiber compaction as a function of aging and cataractogenesis. Exp. Eye Res. 72: 199-214, 2000.
  • Gilliland KO, Freel CD, Lane CW, Fowler WC and Costello MJ. Multilamellar bodies as potential scattering particles in human age-related nuclear cataracts. Mol. Vis. 7, a18, 2001.
  • Freel CD, Gilliland KO, Lane CW, Giblin FJ and Costello MJ. Fourier analysis of cytoplasmic texture in nuclear fiber cells from transparent and cataractous human and animal lenses. Experimental Eye Research. 74: 689-702, 2002.
  • Freel CD, Gilliland KO, Mekeel HE, Giblin FJ and Costello MJ. Ultrastructural characterization and Fourier analysis of fiber cell cytoplasm in the hyperbaric oxygen treated guinea pig lens opacification model. Experimental Eye Research. 76: 405-415, 2003.
  • Gilliland KO, Freel CD, Johnsen S, Fowler WC and Costello MJ. Distribution, spherical structure, and predicted Mie scattering of multilamellar bodies in human age-related nuclear cataracts. Experimental Eye Research. 79: 563-576, 2004.
  • Marsili S, Salganik RI, Albright CD, Freel CD, Johnsen S, Peiffer RL and Costello MJ. Cataract formation in a strain of rats selected for high oxidative stress. Experimental Eye Research. 79: 595-612, 2004.
  • Costello MJ. Cryo-electron microscopy of biological samples. Ultrastructural Pathology. 30: 361-371, 2006.
  • Costello MJ, Johnsen S, Gilliland KO, Johnsen S, Freel CD and Fowler WC. Predicted light scattering from particles observed in human age-related nuclear cataracts using Mie scattering theory. Investigative Ophthalmology and Visual Science. 48: 303-312, 2007.