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Updated: Jun 30, 2026
Intravitreal Injection and Quantitation of Infection Parameters in a Mouse Model of Bacterial Endophthalmitis
Published on: February 6, 2021
Systemic Candida albicans Infection in Mice Causes Endogenous Endophthalmitis via Breaching the Outer Blood-Retinal
Sneha Singh1, Sukhvinder Singh1, Ashok Kumar1,2
1Department of Ophthalmology, Visual and Anatomical Sciences/Kresge Eye Institute, Wayne State Universitygrid.254444.7 School of Medicine, Detroit, Michigan, USA.
Abstract:
Candida albicans is the leading cause of endogenous fungal endophthalmitis; however, its pathobiology studies are limited. Moreover, the contribution of host factors in the pathogenesis of Candida endophthalmitis remains unclear. In the present study, we developed a murine model of C. albicans endogenous endophthalmitis and investigated the molecular pathobiology of ocular candidiasis and blood-retinal barrier permeability. Our data show that intravenous injection of C. albicans in immunocompetent C57BL/6 mice led to endogenous endophthalmitis without causing mortality, and C. albicans was detected in the eyes at 3 days postinfection and persisted for up to 10 days. The intraocular presence of C. albicans coincided with a decrease in retinal function and increased expression of inflammatory mediators (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], MIP2, and KC) and antimicrobial peptides (human β-defensins [hBDs] and LL37) in mouse retinal tissue. C. albicans infection disrupted the blood-retinal barrier (BRB) by decreasing the expression of tight junction (ZO-1) and adherens junction (E-cadherin, N/R-cadherin) proteins. In vitro studies using human retinal pigment epithelial (ARPE-19) cells showed time-dependent activation of eIF2α, extracellular signal-related kinase (ERK), and NF-κB signaling and decreased activity of AMP-activated protein kinase (AMPK) leading to the induction of an inflammatory response upon C. albicans infection. Moreover, C. albicans-infected cells exhibited increased cellular permeability coinciding with a reduction in cellular junction proteins. Overall, our study provides new insight into the molecular pathogenesis of C. albicans endogenous endophthalmitis. Furthermore, the experimental models developed in the study can be used to identify newer therapeutic targets or test the efficacy of drugs to treat and prevent fungal endophthalmitis. IMPORTANCE Patients with candidemia often experience endophthalmitis, a blinding infectious eye disease. However, the pathogenesis of Candida endophthalmitis is not well understood. Here, using in vivo and in vitro experimental models, we describe events leading to the invasion of Candida into the eye. We show that Candida from the systemic circulation disrupts the protective blood-retinal barrier and causes endogenous endophthalmitis. Our study highlights an important role of retinal pigment epithelial cells in evoking innate inflammatory and antimicrobial responses toward C. albicans infection. This study allows a better understanding of the pathobiology of fungal endophthalmitis, which can lead to the discovery of novel therapeutic targets to treat ocular fungal infections.
Insights
Candida albicans causes endogenous endophthalmitis by disrupting the blood-retinal barrier. This study reveals molecular mechanisms and provides models for developing new treatments for fungal eye infections.
Area of Science:
- Ophthalmology and Infectious Diseases
- Mycology and Immunology
Background:
- Candida albicans is a primary cause of fungal endophthalmitis, a serious ocular infection.
- The host's role and molecular mechanisms in Candida endophthalmitis pathogenesis are not fully understood.
- Existing research on the pathobiology of ocular candidiasis is limited.
Purpose of the Study:
- To develop and utilize a murine model for studying endogenous Candida albicans endophthalmitis.
- To investigate the molecular pathobiology of ocular candidiasis and its effect on the blood-retinal barrier (BRB).
- To explore host immune responses and signaling pathways involved in Candida-induced endophthalmitis.
Main Methods:
- Established a murine model of endogenous Candida albicans endophthalmitis via intravenous injection.
- Analyzed retinal function, inflammatory mediator expression, and antimicrobial peptide levels in infected mice.
- Utilized in vitro studies with human retinal pigment epithelial (ARPE-19) cells to examine signaling pathways and cellular permeability.
Main Results:
- Intravenous Candida albicans caused endophthalmitis in immunocompetent mice without mortality, with fungal presence up to 10 days.
- Infection led to decreased retinal function, increased inflammatory mediators (TNF-α, IL-1β, MIP2, KC), and antimicrobial peptides (hBDs, LL37).
- Candida albicans disrupted the BRB by downregulating tight junction (ZO-1) and adherens junction (E-cadherin, N/R-cadherin) proteins, consistent with in vitro findings.
Conclusions:
- This study elucidates the molecular pathogenesis of Candida albicans endogenous endophthalmitis, highlighting BRB disruption.
- Retinal pigment epithelial cells play a key role in initiating innate inflammatory and antimicrobial responses against Candida.
- The developed experimental models offer valuable platforms for identifying novel therapeutic targets and evaluating drugs for fungal endophthalmitis.
