Tell Me How You Cry, and I Will Tell You How You Feel

The series of research stories told by young scholars originates from the PhD Storytelling initiative, in which doctoral students engaged with dissemination and communication experts from the University of Bologna and professionals from UGIS (Italian Union of Scientific Journalists). Gloria Astolfi, PhD student at the Department of Medical and Surgical Sciences, is the author of this article

Tears serve many purposes, and the eyes produce them continuously. In fact, they produce 2 microlitres of tears every minute. Tears are essential to help you see clearly and maintain eye health. They can also help to communicate emotions. A story with a happy ending, a sad breakup, cutting an onion, or speeding along on a bicycle against the wind are all things that can make us cry... Humans are the only animals that cry for love.

TYPES OF TEARS
There are several types of tears, and the eye produces three types:
- Basal tears are always present in the eyes to lubricate, nourish and protect the cornea. They act as a permanent shield between the eye and the external environment, removing dust and debris.
- Reflex tears form when the eyes need to eliminate harmful irritating substances, such as smoke, foreign bodies, or the “lachrymatory factor” released by onions. The eyes release them in greater quantities than basal tears, and they may contain more protective factors, such as antibodies aimed at counteracting potential pathogenic bacteria.
- Finally, there are tears produced in response to emotions—emotional tears are linked to states of joy, sadness, fear, and other emotions.
 
Tears have the vital function of protecting and lubricating the ocular surface. Their production and distribution are strictly regulated by a neural connection to meet the demands of the ocular surface. It is more correctly referred to as the tear film, a thin liquid film that covers the front surface of the eye, which serves various functions.
 
The tear film consists of an aqueous-mucous layer, containing soluble fluids and factors produced by the tear glands, and mucin, a substance secreted by goblet cells, covered with a lipid layer. The set of proteins, glycoproteins and lipids present in tears has the function of maintaining a stable and smooth optical surface. The instability of the tear film and the consequent increase in its evaporation rate cause dysfunctions of the tear system and the occurrence of dry eye disease (DED), which is associated with ocular surface inflammation. DED leads to disturbances in vision quality and to discomfort, or even ocular pain.
 
WHAT ARE TEARS MADE OF?
Our tears have a precise structure. They are evenly distributed over the ocular surface between blinks of the eyelid and consist of three interconnected layers. The first layer, in direct contact with the surface of the cornea and conjunctiva, is the mucous layer, which keeps the surface smooth.
 
The intermediate layer, composed primarily of water, ensures the supply of oxygen and provides the essential nutrients for the ocular surface cells metabolism. These nutrients are rich in numerous dissolved substances, including several proteins such as lysozyme, lipocalin, and lactoferrin. In DED, these proteins are drastically reduced in tears, thereby weakening the defence system of the ocular surface.

Thanks to its optical properties of transparency and its refractive index, the aqueous layer ensures an optically perfect surface, essential for a clear vision.
 
The outermost part, which comes in direct contact with the air and the environment, consists of a lipid layer. Its function is to maintain evaporation of the aqueous component of tears at normal levels. If this increase in evaporation is not compensated for, it can lead to an unbalanced condition, which if constant, becomes chronic. At this point, the patient experiences discomfort perceived as dryness, burning, foreign body sensation, and even pain. As eye health is increasingly gaining attention, maintaining this delicate balance can prevent troublesome symptoms and improve ocular well-being.
 
FEWER TEARS WITH ADVANCING AGE
As we age, basal tear production tends to slow down, which can lead to the development of dry eyes. But age is not the only factor. Contact lens use or certain medications can also contribute to the onset of DED, defined by the Tear Film & Ocular Surface Society (TFOS) as “a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles”.
 
The commonly applied therapy for DED treatment consists of restoring abnormal tears present in the patient through the application of tear replacements, commonly known as “artificial tears”. Eye drops make up almost 90% of the ophthalmic formulations in the market.
 
More specifically, eye drops in the form of solutions and suspensions remain the preferred dosage form thanks to the localised action, relative ease of administration, and patient comfort as opposed to gels, ointments and emulsions. In case of complications, treatment may evolve to include anti-inflammatory agents, tetracyclines, biological eye drops based on blood components, contact lenses, systemic immunosuppressants.
 
Systemic administration of drugs in the eye is severely limited by the presence of the well-known morphological and dynamic barriers of the eye, which can hinder drug penetration into the underlying tissues. In addition, drugs are quickly eliminated through blinking, basal and reflex tearing, and drainage from ocular surfaces before they can penetrate these tissues in effective quantities. As a matter of fact, only a small part of the drug administered in the form of conventional eye drops reaches the anterior ocular tissues (usually between 0.1% and 0.5% of the total dose delivered), thus requiring frequent daily administration to maintain the therapeutic drug concentrations.
 
HOW CAN THIS PROBLEM BE SOLVED?
Drug Delivery Systems are among the various drug release strategies that aim to improve topical ocular bioavailability. They provide a prolonged residence time on the ocular surface. In this way, available drugs have more time to act locally or to penetrate deeper eye tissues and reach their target. In ophthalmology, modern biopolymers offer various alternatives, such as visual improvement, corneal implants and intraocular lenses, to replace damaged parts of the eye. The progress made in synthesis methods and molecular structures has led to the widespread use of synthetic polymers for specific biomedical applications.
 
For my PhD project, I am researching on these subjects, focusing on a medical device based on polymeric materials that would allow the controlled release of molecules and lacrimal components that are deficient in DED, for its treatment. The study stems from a real clinical need and takes into account the great potential that drug delivery systems provide to implement the residence time of eye drops on the ocular surface, increasing their effectiveness.
 
The study is taking place at the Ocular Surface and Translational Research Lab at the Department of Medical and Surgical Sciences of the University of Bologna. The person in charge is Professor Piera Versura, who is also my tutor. The project is also supported through an interdisciplinary collaboration with the Department of Civil, Chemical, Environmental, and Materials Engineering, where the materials were designed, synthesised and characterised by Professor Nadia Lotti’s group at the Laboratory of Macromolecular Synthesis and Materials Characterisation (LAMAC).
 
So far, the project has led to the development of a device designed specifically for the target site, along with the identification of important construction parameters to optimise the efficiency of molecule release for future therapeutic treatments. I trust that I can finalise the device by the end of my PhD, but, as everyone knows, research requires resources, effort, and a lot of time. Therefore, it is not always possible to predict when research will conclude.
 
Especially since there could be other molecules to study for this interesting medical device! This bench-to-bedside translational research is carried out in close collaboration with the clinical team. Professor Luigi Fontana, Director of the Ophthalmology Unit at the University of Bologna and Sant’Orsola Polyclinic, envisions expanding the indications for the use of the device to treat corneal infections in the post-surgical healing of corneal transplant patients. And who knows what else? The true goal of translational research is that you never know where it will lead you!