Systemic Candida albicans Infection in Mice Causes Endogenous Endophthalmitis via Breaching the Outer Blood-Retinal Barrier

Singh, Sneha; Singh, Sukhvinder; Kumar, Ashok

doi:10.1128/spectrum.01658-22

Cited by 5 publications

(6 citation statements)

References 71 publications

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“…Among the causative agents, C. albicans remains a primary contributor to fungal endogenous endophthalmitis, followed by Aspergillus species 10,11 . Recent in vivo research has indicated that systemic Candida albicans infection in mice triggers endogenous endophthalmitis by disrupting the outer blood‐retinal barrier (oBRB) 12 …”

Section: Literature Review and Discussionmentioning

confidence: 99%

“…10,11 Recent in vivo research has indicated that systemic Candida albicans infection in mice triggers endogenous endophthalmitis by disrupting the outer bloodretinal barrier (oBRB). 12 In previous studies, vitreoretinal findings were classified into stages: Stage I, characterized by chorioretinal changes without extension to the vitreous cavity; Stage II, where a fungal mass penetrates the inner limiting membrane and buds in the vitreous cavity; Stage III, associated with vitreous opacity leading to unclear fundal observation; and Stage IV, marked by the complication of retinal detachment (RD) concurrent with Stage III. This staging framework helps determine the optimal timing for surgical intervention.…”

Section: Discussionmentioning

confidence: 99%

“… 10 , 11 Recent in vivo research has indicated that systemic Candida albicans infection in mice triggers endogenous endophthalmitis by disrupting the outer blood‐retinal barrier (oBRB). 12 …”

Section: Literature Review and Discussionmentioning

confidence: 99%

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Bilateral endogenous Candida albicans endophthalmitis following COVID‐19 infection and intravenous antibiotics use: A case report

Wu,

Wang,

Zhang

2023

Clinical Case Reports

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Key Clinical MessageEndogenous fungal endophthalmitis tends to occur in immunocompromised patients, including COVID‐19 infection. For high‐risk populations, timely tissue biopsy, fungal culture, and susceptibility testing can facilitate early diagnosis and treatment, thereby improving the prognosis.AbstractWhile endogenous fungal endophthalmitis is a rare condition, its incidence has recently been on the rise. A 48‐year‐old male presented with complaints of acute visual loss in his right eye for 2 weeks. He had a history of COVID‐19 infection, confirmed by a positive nucleic acid test, and was treated with intravenous antibiotics and glucocorticoids a week before the episode. A comprehensive eye examination revealed significant inflammatory cells floating in the anterior chamber and considerable cloudiness in the vitreous of the right eye, while few vitreous cells were visualized in the left eye. After pars plana vitrectomy (PPV) was performed in the right eye, a vitreous biopsy revealed an intravitreal infection of Candida albicans, which was susceptible to fluconazole. Endogenous fungal endophthalmitis occurs in patients with various underlying systemic conditions, such as those with diabetes, organ transplantation recipients, individuals undergoing chemotherapy, users of corticosteroids and immunosuppressants, AIDS patients, and those engaged in intravenous drug use. In high‐risk populations associated with intravenous antibiotics, the timely identification of one or more well‐defined oval yellow‐white chorioretinal lesions, especially in the posterior pole of the retina, can contribute to an early diagnosis through tissue biopsy, fungal culture, and susceptibility testing. This approach enables targeted antifungal therapy, thereby improving the prognosis of visual function for the patient.

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Section: Literature Review and Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Bilateral endogenous Candida albicans endophthalmitis following COVID‐19 infection and intravenous antibiotics use: A case report

Wu,

Wang,

Zhang

2023

Clinical Case Reports

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“…For the injury group, retinal punches were exposed to hypoxia (2.3% O 2 ) [46][47][48], hyperoxia (40% O 2 ) [49][50][51], hyperthermia (40°C) [52][53][54], hypothermia (33°C) [55][56][57], and methanol poisoning (8 μM formic acid) [58][59][60][61]. In the disease category, retinae were exposed to lipopolysaccharide (LPS, 0.2 μg/mL), mimicking Gram-negative bacterial infection [62][63][64][65]; interferon-γ (1.0 μg/mL), mimicking inflammation [66][67][68]; Candida albicans (100 CFU/mL), mimicking ocular candidiasis [69][70][71][72]; Bartonella henselae (100 CFU/mL), mimicking neuroretinitis [73]; and hyperglycemia (20 mM glucose), mimicking diabetes [74].…”

Section: Cell Type-specific Response To Stress Injury and Disease In ...mentioning

confidence: 99%

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

Norrie,

Lupo,

Shirinifard

et al. 2023

Preprint

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Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development that correlate with changes in gene expression. However, a major limitation of those prior studies was the lack of cellular resolution. Here, we integrate single-cell (sc) RNAseq and scATACseq with bulk retinal data sets to identify cell type specific changes in the chromatin structure during development. Although most genes promoter activity is strongly correlated with chromatin accessibility, we discovered several hundred genes that were transcriptionally silent but had accessible chromatin at their promoters. Most of those silent/accessible gene promoters were in the Muller glial cells. The Muller cells are radial glia of the retina and perform a variety of essential functions to maintain retinal homeostasis and respond to stress, injury, or disease. The silent/accessible genes in Muller glia are enriched in pathways related to inflammation, angiogenesis, and other types of cell-cell signaling and were rapidly activated when we tested 15 different physiologically relevant conditions to mimic retinal stress, injury, or disease in human and murine retinae. We refer to these as pliancy genes because they allow the Muller glia to rapidly change their gene expression and cellular state in response to different types of retinal insults. The Muller glial cell pliancy program is established during development, and we demonstrate that pliancy genes are necessary and sufficient for regulating inflammation in the murine retina in vivo. In zebrafish, Muller glia can de-differentiate and form retinal progenitor cells that replace lost neurons. The pro-inflammatory pliancy gene cascade is not activated in zebrafish Muller glia following injury, and we propose a model in which species-specific pliancy programs underly the differential response to retinal damage in species that can regenerate retinal neurons (zebrafish) versus those that cannot (humans and mice).

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“…However, ensuring optimal therapeutic outcomes has frequently involved a comprehensive assessment of the ocular fundus, especially since identifying ocular candidiasis dictates a pivot towards utilizing agents, such as Fluconazole, that traverse the BRB effectively [68,69]. In clinical practice, unaddressed ocular candidiasis is considered a credible threat to patient survival by maintaining a continual source of infection [70]. These common practices are more recently confirmed by recent guidelines about performing ocular fundus evaluations.…”

Section: Systemic Fungal Infectionsmentioning

confidence: 99%

From Bedside to Diagnosis: The Role of Ocular Fundus in Systemic Infections

Visioli,

Zeppieri,

Iannucci

et al. 2023

JCM

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In this comprehensive review, we delve into the significance of the ocular fundus examination in diagnosing and managing systemic infections at the bedside. While the utilization of advanced ophthalmological diagnostic technologies can present challenges in bedside care, especially for hospitalized patients confined to their beds or during infection outbreaks, the ocular fundus examination often emerges as an essential, and sometimes the only practical, diagnostic tool. Recent discussions have highlighted that the role of an ocular fundus examination might not always be advocated as a routine diagnostic procedure. With this context, we introduce a decision tree tailored for assessing the ocular fundus in inpatients with systemic infections. We also present an overview of systemic infections that impact the eye and elucidate key signs detectable through a bedside ocular fundus examination. Targeted primarily at non-ophthalmology clinicians, this review seeks to offer a comprehensive insight into a multifaceted approach and the enhancement of patient clinical outcomes.

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Systemic Candida albicans Infection in Mice Causes Endogenous Endophthalmitis via Breaching the Outer Blood-Retinal Barrier

Abstract: Patients with candidemia often experience endophthalmitis, a blinding infectious eye disease. However, the pathogenesis of Candida endophthalmitis is not well understood.

Cited by 5 publications

References 71 publications

Bilateral endogenous Candida albicans endophthalmitis following COVID‐19 infection and intravenous antibiotics use: A case report

Bilateral endogenous Candida albicans endophthalmitis following COVID‐19 infection and intravenous antibiotics use: A case report

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

From Bedside to Diagnosis: The Role of Ocular Fundus in Systemic Infections

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