Evolution of the ocular immune system

Abstract

The evolution of the ocular immune system should be viewed within the context of the evolution of the immune system, and indeed organisms, as a whole. Since the earliest time, the most primitive responses of single cell organisms involved molecules such as anti-microbial peptides and behaviours such as phagocytosis. Innate immunity took shape ~2.5 billion years ago while adaptive immunity and antigen specificity appeared with vertebrate evolution ~ 500 million years ago. The invention of the microscope and the germ theory of disease precipitated debate on cellular versus humoral immunity, resolved by the discovery of B and T cells. Most recently, our understanding of the microbiome and consideration of the host existing symbiotically with trillions of microbial genes (the holobiont), suggests that the immune system is a sensor of homoeostasis rather than simply a responder to pathogens. Each tissue type in multicellular organisms, such as vertebrates, has a customised response to immune challenge, with powerful reactions most evident in barrier tissues such as the skin and gut mucosa, while the eye and brain occupy the opposite extreme where responses are attenuated. The experimental background which historically led to the concept of immune privilege is discussed in this review; however, we propose that the ocular immune response should not be viewed as unique but simply an example of how the tissues variably respond in nature, more or less to the same challenge (or danger).

Fig. 1. Symbiosis and the Holobiont.

Symbiosis and the Holobiont: Host genes plus microbiome genes constitute the holobiont which maintains homoeostasis (immunological tolerance) through symbiosis, mediated by immune regulatory molecules such as indoleamine (IDO), the aryl hydrocarbon receptor (Arh-R), interleukin 33 (IL33) in host cells and short chain fatty acids from the microbiota. The CNS (the eye and the brain) controls homoeostasis by feedforward and feedback interactions through neural and signalling networks which contribute to important regulatory mechanisms such as blood CNS barriers (see later text for details). Host metabolism plays a major role in maintaining homoeostasis: disturbance of homoeostasis is fuelled through an increase in glycolysis while homoeostasis is maintained through oxidative phosphorylation (Ox-Phos). (Figure complied from images provided by istockphoto.com).

Fig. 2. The Tree of Life.

Tree of Life indicating estimated timing of appearance of innate and adaptive immunity during evolution. Adaptive immunity coincides with appearance of vertebrates while evidence of innate immunity is present in unicellular organisms. (By courtesy of Encyclopædia Britannica, Inc., copyright 2021; used with permission.).

Fig. 3. Evolution of life Forms with Photosensitive Organelles.

Basic summary of the evolution of life forms with photosensitive organelles such as Euglena which aid, via phototaxis and diurnal rhythms, the emergence of multicellular animals and eventually bilateralia in which various light-gathering and receptive organs (‘eyes’) arise in forms of life in which there are two eyes which have connections to a central neural network (brain). Time scale on left is very approximate. [for an extensive consideration of the early evolution of photoreception, opsins and the evolution of the vertebrate eye, with reference to ciliary and rhabdomeric photoreceptors see refs. 98, 99].

Fig. 4. Histopathology of Toxoplasma Cysts in the Mouse Retina.

A Light micrograph of mouse retina showing a Toxoplasma cyst residing in the inner retina with no obvious signs of an inflammatory/host response. B low power electron micrograph showing a Toxoplasma cyst containing many bradyzoites surrounded by host glial and neural cells of the inner nuclear layer. C high power electron micrograph of two bradyzoites. In some mice (not shown) in this model of congenital toxoplasmosis [100] there was marked inflammation in the retina [101].