Research Overview

Dr. Oscar Candia's general interests involve the characterization of basic physiological phenomena in ocular epithelia that are related to membrane permeability, and ionic and fluid transport. During the past few years, studies focused on transport mechanisms in the rabbit and bovine ciliary epithelium, the rabbit crystalline lens and cornea, and rabbit and porcine conjunctivae. This work involved measurements of transepithelial electrical parameters and radiolabeled fluxes of ions and water; immunoblotting and immunohistochemical approaches to characterize various transporters, channels and membrane receptors; and RT-PCR, to identify receptor subtypes.

Studies on the ciliary body modeled the ionic transport properties of this two-cell-layered epithelium, which has a critical role in the production of the aqueous humor that circulates through the chambers of the anterior segment of the eye and maintains the intraocular pressure.

Recent lens experiments examined the distribution the Na-K-2Cl cotransporter within the lens and factors that regulate its activity. This symport is relatively inactive under physiological conditions in the freshly isolated intact lens, but can be activated by hypertonic conditions, as well as various factors used to maintain lens cells in culture. In the rabbit lens, a description of ionic currents that enter and leave the lens that may serve as the driving force for an internal fluid circulation was provided. Furthermore, using mathematical models developed in his laboratory, it was found that fluid moves out and into the lens in a reversible manner during accommodation. Studies on the conjunctival epithelium have begun a characterization of the likely neuronal regulation of transepithelial ion transport. It is well recognized that the conjunctiva is extensively innervated. The underlying rationale for such is a quest for elaborating the secretory functions of the epithelium under the premise that such efforts might have utility in ameliorating complications from dry-eye diseases. Because of its relatively large surface area, active chloride transport by the conjunctiva with accompanying fluid secretion may contribute to a significant fraction of tear production (normally provided in healthy individuals by the lacrimal gland).

In addition to the Cl secretory activity of the conjunctival epithelium, the tissue also manifests a Na absorptive process in the apical-to-basolateral direction that is mediated by electrogenic Na-linked co-carriers for glucose and amino acids. Thus, depending upon which system is dominant, conjunctival ionic transport could potentially be a driving force for either fluid secretion into, or absorption from, the tear film. With the conjunctiva, our group was the first to identify the water channel, aquaporin type 5 (AQP5) on the tear-interfacing apical surface.

In most recent work, Dr. Candia in collaboration with Dr. Rosana Gerometta of Universidad Nacional del Nordeste, Corrientes, Argentina, developed a corticosteroid-induced ocular hypertension model in cow and sheep. This work showed that sheep are an especially good model for steroid-induced glaucoma, and suitable for testing anti-glaucoma drugs. The importance of the sheep animal model was recognized by the New York Academy of Medicine, which awarded Dr. Candia the 2009 Lewis Rudin Glaucoma Prize for the best glaucoma publication of the year.

Using the sheep model, additional work suggested that understanding the hypotensive mechanism(s) of anecortave acetate could be important to the design of novel interventions for managing primary open-angle glaucoma. This suggestion received a positive editorial comment that was published in tandem with Dr. Candia's report in Archives of Ophthalmology.

Moreover, other collaborations on the sheep model 1) explored the possibility of applying a gene therapy approach for steroid-induced ocular hypertension, using an adenoviral vector carrying an inducible metalloproteinase human gene (MMP1), and 2) examined the morphological changes that occur in the trabecular meshwork aqueous outflow pathway in response to topical glucocorticosteroid instillations.