Fluid Movement across Conjunctiva: Stimulation and Regulation

Summary

Principal Investigator: O A Candia
Abstract: We have previously characterized the isolated rabbit conjunctiva as an epithelial model of Na absorption and CI secretion. Our hypothesis was that these transport mechanisms, by providing the driving forces for fluid movement across the tissue, could enable the conjunctiva to either absorb fluid from, or contribute fluid to, the aqueous layer of the tear film. This was demonstrated with direct experiments using the rabbit epithelium. Our current hypothesis is that the human conjunctiva may also possess transporters that enable it to absorb Na and secrete CI with the consequent fluid absorption or secretion. For this fluid flow to occur, the conjunctiva must have (as most fluid transporting epithelia do) water channels, which are usually different in the apical and basolateral domains. We thus propose to identify with biochemical and histochemical protocols, the electrolyte transporters and water channels (aquaporins) in the human conjunctiva relevant towards the movement of fluid flow across the epithelium. Because receptor-mediated responses are atypical in rabbit conjunctiva, assays similar to those in human will be done on murine and porcine tissues to determine the best model for fluid transport in the human conjunctiva. Since aquaporins (AQPs) play a crucial role in fluid transport, and our experiments have shown that anisotonic conditions and cAMP-elevating agents can modify water permeability, protocols to understand the regulation of water permeability in murine and porcine tissues will be implemented. Biochemical, histochemical and functional experiments will be conducted on mice, rat and pig conjunctivae. From the determination of the transporters, the AQPs, and the functional physiological experiments that can be done on the conjunctiva of the selected animal models, a theoretical model for the fluid movement across the human conjunctiva will be proposed. From these studies we expect to expand the understanding of the physiology of the mammalian conjunctival epithelium, and provide evidence that direct or receptor-mediated stimulation of ionic transport mechanisms will result in fluid secretion towards the tear film. These studies may provide the groundwork for the design of future treatment modalities for dry-eye syndromes.
Funding Period: 2004-09-01 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Regulation of water permeability in rabbit conjunctival epithelium by anisotonic conditions
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, 100th St and 5th Ave, New York, NY 10029, USA
    Am J Physiol Cell Physiol 290:C1168-78. 2006
  2. ncbi Identification and localization of aquaporin 5 in the mammalian conjunctival epithelium
    Handy Oen
    Exp Eye Res 83:995-8. 2006
  3. pmc IBMX-elicited inhibition of water permeability in the isolated rabbit conjunctival epithelium
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Exp Eye Res 86:480-91. 2008
  4. pmc Fluid transport phenomena in ocular epithelia
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Prog Retin Eye Res 27:197-212. 2008

Scientific Experts

  • O A Candia
  • Handy Oen
  • Lawrence J Alvarez
  • Helen C Turner
  • Pang Cheng

Detail Information

Publications4

  1. ncbi Regulation of water permeability in rabbit conjunctival epithelium by anisotonic conditions
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, 100th St and 5th Ave, New York, NY 10029, USA
    Am J Physiol Cell Physiol 290:C1168-78. 2006
    ..Presumably both apical and basolateral membranes can downregulate their water permeabilities as part of a protective mechanism to help maintain cell volume...
  2. ncbi Identification and localization of aquaporin 5 in the mammalian conjunctival epithelium
    Handy Oen
    Exp Eye Res 83:995-8. 2006
  3. pmc IBMX-elicited inhibition of water permeability in the isolated rabbit conjunctival epithelium
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Exp Eye Res 86:480-91. 2008
    ..g., PDE inhibition)...
  4. pmc Fluid transport phenomena in ocular epithelia
    Oscar A Candia
    Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Prog Retin Eye Res 27:197-212. 2008
    ....