Immune Cell Presence on the Crystalline Lens in Uveitis

Article: Reimagining Immunity in the Eye
Source: Thomas Jefferson University
Published: December 8, 2021 

Despite being susceptible to a range of potential threats—whether they come from pathogens, chemicals, radiation, or general oxidative damage—it is surprising that ocular tissues such as the cornea, crystalline lens, and retina are thought to be immune privileged, that is, lacking immune cells. So how do these critical tissues protect themselves? Closer investigation by researchers in previous work revealed, for example, that mice engineered to lack a key protein for crystalline lens formation showed immune cells trying to fix the resulting malformed lens. Other researchers observed immune cells in the cornea after damage to the lens, and vice versa immune cells arriving at the lens surface, acting like sentinels to protect this tissue after damage to the cornea (the external ocular surface). In a new study, researchers at Thomas Jefferson University show that immune cells respond to the lens not only after acute eye injury but also in chronic inflammation. Using high-resolution microscopy and a mouse model of uveitis, or inflammation to the middle layer of the eye, the researchers studied the role of immune cells in relation to cataracts associated with uveitis. 

Immune cells observed at the lens capsule surface (top)
and integrated into the lens capsule (bottom)

Unlike the sentinels seen after ocular surface injury, the researchers report, "In this case, it was like a battering ram. There were dozens of immune cells, and different types of them, including T-cells and macrophages. It’s clearly a robust immune response and could reflect in part that inflammation in uveitis is so severe." Similarly, it was previously thought that the lens capsule surrounding the lens protects it from the increase in immune cells that populate the aqueous and vitreous chambers during active uveitis. However, high-resolution confocal z-stacks and scanning electron microscopy revealed that immune cells were actually integrated into the lens capsule, increasing not only in number but also in depth (invasion) as the uveitis progressed. Moreover, the immune cells were observed to be able to penetrate the thick lens capsule, infiltrate into and embedding themselves in the lens tissue. Although most of the cells were gone as the uveitis began to resolve, some of these immune cells remained integrated into the lens capsule and lens tissue. Underscoring the complexity of the presence of immune cells in the eye, a topic that has thus far been understudied, the senior author of the study explains, "Till now, the mechanisms for damage that happen in this region of the eye after uveitis have been poorly understood. For the first time, we’ve been able to provide evidence that immune cells could be driving this damage, particularly to the lens.”

My rating of this study: ⭐⭐⭐⭐

DeDreu J, Pal-Ghosh S, Mattapallil MJ, et al. "Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule." The FASEB Journal.  4:1360. 7 December 2021. https://doi.org/10.1096/fj.202101098R