Table 3 Most abundant proteins identified in the TF of the evaluated cats and their respective functions.

Allergen Fel d 4

Cat-specific allergen lipocalin, which composes two of the ten feline allergens found in their body fluids and secretions, although not yet described in tears. Responsible for allergic reactions of other mammals (especially humans) to felines. Homologous to the main equine allergen, Equ c1. Its biological function in felines remains unknown [48,49,50].

Major allergen 1

Major feline allergen, responsible for up to 90% of the IgE-mediated response in allergic reactions to cats. Its biological function in felines, like lipocalin Feld 4, remains unknown. Since it has not yet been described in the tears of domestic cats, it is another possible source triggering allergic processes to felines, as well as Fel d 4 [48,49,50,51].

Serum albumin

One of the 1500 proteins already reported in tear film of several species. It acts in local antimicrobial defense, as a marker of the integrity of the blood-ocular barrier and maintenance of tear osmolarity [2, 11, 15, 18, 33, 52, 53].

Aldehyde dehydrogenase

It had been reported in human tear samples. Some subfamilies of this enzyme are present in the cornea and lens and are part of the defense mechanism against injuries caused by ultraviolet rays, maintaining the integrity of these structures. In addition, they help maintain cellular homeostasis, as they protect cells against reactive oxygen species, and consequently from oxidative stress, as well as protect the lens from cataract formation [20, 54, 55].

Lactoperoxidase

An enzyme present in several mammalian bodily fluids, such as tears, with main antimicrobial activity. Furthermore, it protects cells against peroxidative effects and carcinogens [56].

Inhibitor of carbonic anhydrase

It has already been reported in several bodily fluids, such as tears, including those already described in the eye system of dogs. It binds to and inhibits some isoforms of carbonic anhydrase. Anhydrase, in turn, helps maintain the pH of the TF, in addition to protecting the corneal epithelium against aggression [57, 58].

Deleted in malignant brain tumors 1 protein

A glycoprotein that can bind to mucosal defense proteins, such as IgA, lactoferrin and albumin, participating in the innate immune response. Since it also binds to the C1q fraction of complement, it indirectly participates in the response to pathogens, which is important for the inflammatory response against invading microorganisms. It has already been described in the TF of humans [20, 59].

Haptoglobin

Its main function in the body is to bind to hemoglobin dimers that are released into the circulation after hemolysis. Furthermore, it is part of the acute phase proteins, thus participating in immunomodulation. In humans there is an increase in infectious diseases such as conjunctivitis [60].

Glutathione S transferase

Acts as an antioxidant in the eye system [61, 62].

Polymeric immunoglobulin receptor

This glycoprotein has already been described in tear samples of humans. It is crucial for the effectuation of humoral and cellular immune responses and for the elimination of antigens, since it is through its connection that several biological responses are performed, such as phagocytosis, capture of immune complexes and release of inflammatory mediators [20, 63].

Retinal dehydrogenase 1

It helps to preserve the integrity of vision, as well as minimizing the effects of oxidative stress, acting as an antioxidant for the cornea [55, 64].

Immunoglobulin heavy variable

The most abundant heavy-chain immunoglobulin in the TF is IgA, along with lysozyme, lactoferrin, and lipocalin. Its main function is to defend the ocular mucosa against pathogens [32, 65].

Selenium-binding protein

It acts to regulate oxidative stress and is secreted by the lacrimal gland. Studies in humans who have keratoconjunctivitis sicca indicate that the reduction of selenium expression by the lacrimal glands leaves the cornea of these patients exposed to oxidative damage [3, 66].

Alpha-enolase

Glycolytic enzyme expressed in most cells, important in autoimmune diseases, cancer and fungal diseases. Studies analyzing the tear film in humans with dry eye syndrome revealed an increase in this protein in affected patients [67].

14–3-3 protein sigma

A family of different isoforms of proteins secreted by the cornea and conjunctiva, important for the regulation of metabolism and cell cycle, as well as for apoptosis, protein transport, and transcription [4].

Malate dehydrogenase

Although not secreted by the lacrimal gland, this enzyme can be released into the TF after damage to the corneal and conjunctival epithelium, even by collection using the Schimmer test. It is important for cell transduction and metabolism [68,69,70].

Serotransferrin

An important glycoprotein for the structural integrity of the epithelial cells that make up the ocular system, as well as protection against pathogens [71].

Keratin

It is present in the epithelial and myoepithelial cells that make up the lacrimal and meiosis glands, interacting with the lipid layer of the tear film [72].

Phosphoglycerate mutase

In mammalian tissue, type B can be found in the retina. In a proteomic study of retinal samples of myopia in guinea pigs, it was observed that of the retinal proteins expressed in myopic eyes, the phosphoglycerate mutase was one of those that presented a reduction in its expression when compared to the control group [73]. According to the authors, it is important for cell metabolism and regulation of biological processes [73, 74].

Elongation factor 1-alpha

A binding protein, essential for protein synthesis, also acting in the regulation of actin cytoskeleton, protein degradation and apoptosis, in addition to being reported as a promoter of viral replication [75, 76].

Alpha cristallin A, B

Most abundant protein components in mammalian eye lenses, helping to maintain lens transparency; present in the cells of the lacrimal gland ducts. Mutations in these can cause cataracts. Furthermore, they also protect against oxidative stress and high temperatures. Alpha B present in the TF may originate from corneal degeneration or from the epithelial cells of the conjunctiva [77, 78].

Annexin A1

Regulating/mediating glucocorticoid protein with anti-inflammatory action. In research carried out with rats, it was concluded that annexin also has anti-inflammatory action on ocular inflammation, especially in cases of uveitis. Studies carried out with humans concluded that it is physiologically present in tears [79,80,81].

Actin

Cell cytoskeleton component [24].

Gelsolin

Important for cell locomotion and phagocytosis. Responsible for cell differentiation, epithelial cell regeneration and apoptosis. Expressed in all tissues of the ocular system, secreted by TF [26, 27].

Ceruloplasmin

Studies indicate there is high affinity interaction with lactoferrin [29].

Ig Kappa; Ig Lambda

Immunoglobulin components of the immune response, present in the cornea, probably derived from the serum [30].

Lactotranferrin

Anti-inflammatory and antimicrobial activities and an important role in innate immunity, helping to fight pathogens and maintain the health of the eye system; also acts to protect eye tract cells against oxidative damage [3, 33, 34].

Ovostatin

Important metalloproteinase for the degradation and reabsorption of extracellular matrix components [36].