Lee NG, Kim LA, Freitag SK.
The role of genetics in the pathogenesis of periocular cutaneous neoplasms: implications for targeted therapy. Semin Ophthalmol 2013;28(5-6):267-74.
AbstractIn the past, cutaneous malignancies of the periocular region were primarily treated surgically with few other options. As the genetic bases of these tumors have become elucidated, targeted therapies aimed specifically at pathways that are felt to be responsible for cellular proliferation and uncontrolled growth have emerged with new promise. This review contains a summary of the various genetic implications of cutaneous neoplasms as well as their corresponding targeted systemic therapies.
Lee HJ, Colby KA.
A review of the clinical and genetic aspects of aniridia. Semin Ophthalmol 2013;28(5-6):306-12.
AbstractAniridia classically presents with a bilateral congenital absence or malformation of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop visually significant pre-senile cataracts and keratopathy. Additionally, they are at high risk for developing glaucoma. Classic aniridia can be genetically defined as the presence of a PAX6 gene deletion or loss-of-function mutation that results in haploinsufficiency. Variants of aniridia, which include a condition previously referred to as autosomal dominant keratitis, are likely due to PAX6 mutations that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK) is a progressive and potentially debilitating problem affecting aniridic patients. The current treatments for AAK are to replace the limbal stem cells through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future therapies for AAK may be aimed at the genetic modification of corneal limbal stem cells.
Lee HS, Schlereth S, Khandelwal P, Saban DR.
Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process. PLoS One 2013;8(9):e75769.
AbstractA reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.
Liu Y, Rhee DJ.
Acute bilateral angle closure. JAMA Ophthalmol 2013;131(9):1231-2.