Introduction
Endophthalmitis is a vision-threatening condition that requires prompt diagnosis and treatment to prevent vision loss.1 Bacterial endophthalmitis, with an estimated incidence between 0.07% and 0.3%, is among the most severe complications of cataract surgery, one of the most common surgical procedures performed in the aged population worldwide.2 Moreover, the incidence of endophthalmitis is likely to grow in the coming years due to increasing use of multiple intravitreal injections for the treatment of age related macular degeneration and diabetic retinopathy.3 The incidence of endophthalmitis after ocular surgery or injection is 0.016% to 0.46%,3-8 and after trauma is 0.9% to 17%.3, 9-11 Among the bacterial pathogens, most postoperative endophthalmitis cases are caused by Gram-positive staphylococci, with Staphylococcus epidermidis and Staphylococcus aureus accounting for 70% and 10% of all cases, respectively.1 Compared to S. epidermidis, S. aureus is a more pathogenic bacterium and causes severe inflammation and destruction of the retina, resulting in worse visual prognosis even with treatment.12 As such, S. aureus infections are a major public health concern due to the bacterium’s ubiquitous presence and increasing resistance to antimicrobial agents.13, 14 In the past, methicillin resistant S. aureus (MRSA) was confined to hospital-related infections, but now it has been identified with increasing incidence in community-acquired infections.15 Therefore, the overall incidence of MRSA infections has increased in recent years. Infections with community-associated MRSA subtypes can lead to aggressive infections in the eye even in patients with no previous hospital exposure.16 Since the publication of the Endophthalmitis Vitrectomy Study in 1996, several recent studies have reported an increased incidence of MRSA endophthalmitis after cataract surgery.17, 18 This serious infection may not be preventable by the use of preoperative fluoroquinolone antibiotics.17 Although this class of powerful antibiotics covers a broad spectrum of organisms, they seem to be less effective against MRSA. To date, vancomycin has been regarded as the ultimate drug for the treatment of endophthalmitis caused by MRSA. However, in the past few years the appearance of vancomycin-resistant S. aureus strains in hospital settings, food and within the environment has become an important public health concern.19, 20
In this context, one long-term goal would be to understand the regulation of retinal innate immunity in endophthalmitis. The knowledge derived from such studies would conceivably serve as a cornerstone for the identification of target candidates for intervention. Recognition of microbial infection and initiation of the host defense responses are controlled by multiple mechanisms. The host innate immune system uses a series of pattern recognition receptors (PRRs) to detect the presence of pathogens, thus allowing rapid host defense responses toward invading microbes.21 A major class of such receptors is a family of proteins, famously known as “Toll-like receptors” (TLRs).22 Previous studies from our laboratory and others have revealed an important role of TLRs in mediating innate immune responses at the ocular surface.13, 23-27 Although the expression and function of TLRs in many tissues have been studied extensively, studies have just begun to investigate their role in the retina and various retinal diseases. Earlier retinal pigment epithelial (RPE) cells have been shown to express TLR2, TLR3, TLR4 and TLR9.28 However, many questions fundamental to the understanding of retinal innate immunity remain elusive. For example: which cell types in the retinal tissue are involved in the recognition of invading pathogens in endophthalmitis? Another pertinent question has been if the TLR innate immune system functionally exists and operates in the retina? If yes, which TLRs are involved and how do they orchestrate among themselves? How might retinal cells, most importantly microglia and Müller cells, respond to bacteria or TLR ligand(s) challenge?
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Several mouse models of bacterial endophthalmitis and cultured retinal cells have been utilized to understand host-pathogen interaction in endophthalmitis and to address some of these questions. In this review, we shall discuss the myriad roles Müller cells may play in different immunological backgrounds, with reference to bacterial endophthalmitis.
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