Graduate student Deepa Talreja wins prize at Vision Research Workshop

Graduate student Deepa Talreja, of the Biological and Biomedical Sciences PhD Program, won first prize and a $500 award at the Vision Research Workshop hosted by the Kresge Eye Institute. Coauthors on the presentation are Satish Walia of the Department of Biological Sciences and Ashok Kumar of the Department of Ophthalmology at Kresge. Talreja has two first-author publications appearing in 2014, one in Investigative Ophthalmology & Visual Science (Volume 15, Pages 2392-2402) and another in Current Eye Research (Volume 39, Pages 695-704). Her award winning abstract is reproduced below.

Toll-like receptor 2 mediates retinal pigmented epithelial (RPE) cell innate responses to Candida albicans.
Authors: Deepa Talreja, Satish K. Walia, and Ashok Kumar
Dept Biological Sciences, Oakland University, Rochester, MI
Kresge Eye Institute, Wayne State University, Detroit, MI

Purpose: Candida albicans is the leading cause of endogenous fungal endophthalmitis (FE) in immunocompromised individuals. Although the pathogenesis of FE is not well known, the retinal pigment epithelium (RPE), a key component of the blood retinal barrier (BRB) is thought to play a role in retinal innate defense in endogenous endophthalmitis. The aim of this study is to determine the innate immune responses of RPE cells towards C. albicans.
Methods: Immortalized human (ARPE-19) and primary mouse RPE cells were challenged with C. albicans and the time course studies were performed. Pathogen-induced expression of TLRs and pro-inflammatory cytokines/chemokines were assessed by qRT-PCR, whereas their expression at protein levels was determined by ELISA or Western blot. Activation of down-stream signaling pathways (NF-κB, p38 and pERK) was assessed by Western blotting. The antimicrobial activity of the activated RPE was tested using pathogen killing assays.
Results: Both ARPE-19 and primary RPE cells express all TLRs 1-10 constitutively, albeit at differential levels. However, C. albicans induced the expression of TLR 2, 5 and 6 in a time-dependent manner with marked upregulation of TLR2. The downstream signaling pathways (NF- κB, p38 and ERK) were also activated in RPE cells challenged with C. albicans. Concomitant with activation of NF-κB and MAPKs, transcriptional expression of TNF-α, IL-8, IL-6, IL-1β, beta-defensin-1, 2, 3, and LL-37 were induced in RPE cells. The treatment of RPE cells with TLR2 neutralizing antibody attenuated C. albicans-induced inflammatory responses. The antimicrobial assay revealed increased anti-fungal activity of RPE conditioned media.
Conclusions: These results indicate that RPE cells possess the ability to recognize and respond to the fungal pathogens and TLR2-signaling mediate innate responses to C. albicans.