Hormones and Dry Eye Syndrome

An Update on What We Do and Don't Know

Eduardo Melani Roch; Flavio Mantelli, Luis Fernando Nominato; Stefano Bonini


Curr Opin Ophthalmol. 2013;24(4):348-355. 

In This Article

Gene Therapy for LG

Various hormones are essential contributors for maintaining LG function. Such control sustains tear film composition and volume needed to nourish and protect the anterior ocular surface.[2] Under several different conditions involving hormonal expression dysregulation, medications can induce hormonal replacement needed to restore the hormonal balance, required to inhibit or suppress immune responses.

In situations where only chronic and/or local hormonal doses can meet these needs, gene therapy, however, may be a viable alternative. Such an approach has been used in different animal models to deliver a gene of interest with a viral vector.[71,72,73] The possibility of using noncritical-for-life organs like salivary and lacrimal glands has been shown to be well tolerated and efficient for local and systemic therapeutic purposes in these models.[74]

Growth hormones, along with erythropoietin expanding-4 (a promoter of insulin secretion), were transfected into salivary glands. Insulin expression was detected in saliva or blood of mice.[75,76] In animal models of dry mouth and dry eye induced by radiotherapy, the treated group presented with reduced frequency of oral ulcers, improved cornea epithelial thickness, and restoration of the production of saliva and tears.[77]

The concept of applying virus vector carried gene therapy to treat ocular surface diseases, using the lacrimal gland as an endogenous bioreactor, was recently evaluated. The tropism of certain serotypes of adeno-associated virus vector for specific target lacrimal gland cells, and the expression of the luciferase protein without histological or functional damage was described.[78]

These findings suggest that the lacrimal gland is a feasible target for gene therapy in cases of DES related to hormonal dysfunction. Current indications are that hormonal production could be induced in this peripheral organ without compromising local or systemic health. Such therapy also has the potential to be of benefit to other local or regional tissues.