Therefore, the underlying philosophy of translational research is that of the timely application of results for the benefit of patients.

The most significant translational research products of the last three years (2021-2023)

The experimental research activities undertaken by the glaucoma research unit have wide repercussions in the -translational field. The development of in vitro cellular models, as well as the understanding of biochemical mechanisms of regulation of macromolecules to biological pathways responsible for the homeostasis of retinal ganglion cells and the optic nerve, are of central importance to hypothesize therapeutic strategies or to support the functionality of these anatomical districts that are typically affected by the onset and progression of glaucoma.

The research carried out has also allowed the development of further approaches of increasing complexity (in the application and publication phase), especially in the field of clinical proteomics, taking advantage of the recent launch of the Institute’s dedicated facility

The state of the art regarding the role of ubiquitination, one of the main post-translational modifications of proteins, in the pathogenesis of glaucoma has been deepened. Ubiquitin (Ub) is a small protein enzymatically conjugated to proteins that plays a central role in modulating their turnover and biological function.

These projects are fully integrated into biomarker discovery and validation pipelines, with the aim of improving one of the unmet needs in the clinical management of glaucoma, namely the identification of reliable and early markers of development and progression.

The study undertaken of molecules with neuroprotective potential such as carnosine and citicoline has the important translational impact of the potential development of new therapeutic approaches able to accompany ocular hypotensive therapy for the stabilization of visual damage in patients with progressive glaucoma. The functional diagnosis of glaucoma, whose gold standard to date is represented by the standard perimeter, is all burdened by significant limits in the early diagnosis and detection of damage progression. The clinical impact of the studies undertaken in this area has the important role of providing data that can promote the development of new algorithms and examination strategies that can improve the sensitivity and specificity of the perimeter and promote the early diagnosis of the disease and its progression. In the same way, the safety and efficacy results of studies in the surgical field have the important clinical impact linked to the possibility of optimizing the new minimally invasive techniques and improving patient selection with the final idea of customizing the surgical indication according to the patient’s clinical profile.

The anterior segment research unit carries out activities in the field of corneal and ocular surface diseases and cataract surgery, specifically:

• validation of a new model of corneal specular microscopy that allows in vivo microscopic visualization of the entire cornea, contributing to the diagnosis of major corneal diseases (Cell/Check konan), an instrument currently unique in Italy;
• laboratory research concerning the products of metabolomics and the presence of hormone receptors on tissues implanted during lamellar corneal surgery, specifically DMEK (descemet membrane endothelial keratotoplasty), DSAEK (descemet stripping automated endothelial keratoplasty) and DALK (Deep Anterior Lamellar Keratoplasty). These studies will allow us to better understand the pathogenesis of corneal dystrophies.
• Studies concerning the efficacy of new artificial lens models with a depth of elongated focus that allow visual rehabilitation after cataract surgery with the possibility of frontal lens elimination.

In the three-year period 2021-2023, the multidisciplinary and interdisciplinary laboratory was dedicated to applied research, developing potential collaborations in order to be able to license the two patents surfAL and ACkit. In particular, the ACkit patent has been considered in national and international projects, and of interest for future lab-on-chip to be spent also on microgravity projects preparatory to future missions in space.

In the context of experimental research on the medical retina, the projects undertaken have made it possible to achieve significant goals in the translational field, in particular for diabetic retinopathy.

In vitro research (illustrated by the description of the individual publications) has in fact made it possible to identify and validate (further studies on mouse models, not yet published, have confirmed the molecular implantation) new mechanisms for regulating the pro-inflammatory polarization of Muller’s glia and the consequent effector phase. Enzymes (calmodulin and proteasome), as well as effectors (interleukin-8), are targets of absolute pharmacological interest for the development of unconventional therapies for diabetic retinopathy. Protocols for animal model testing are currently being analysed and rationalised.

In addition, the recent launch of the Institute’s proteomics facility, combined with the approval by the Ethics Committee of a study protocol, is allowing the development of biomarkers discovery and validation pipelines on biological samples isolated from patients suffering from the main retinal-choroidal diseases.

As part of the experimental research of the surgical retina, the study with experimental models of the fluid dynamics of the vitreous body is aimed at evaluating the efficacy and safety of the current vitreoretinal surgery instruments with the possibility of proposing improvements thereof. In a recent study, a careful evaluation of the retina-buffering medium interaction made it possible to explain the causes of recurrence of inferior retinal detachment, of the emulsification of silicone oil, contributing to the development of better vitreous substitutes (doi: 10(8):22. doi:10.1167/tvst.10.8.22). Another study showed that increasing the shear rate does not produce proportionally smaller glass fragments. In order to reduce retinal traction during vitrectomy it is necessary to obtain an instantaneous invariable flow through the cutter port (doi: 10.1167/tvst.11.3).

In the field of ocular oncology and toxicology, studies have been carried out aimed in particular at:

• identifying new diagnostic and prognostic factors in intraocular fluids and ocular tissues, in intraocular and systemic neoplastic and degenerative diseases, following the most innovative concepts of precision medicine.
• evaluating the role of multimodal diagnostics in the study of side effects secondary to antineoplastic therapies, both at the level of the anterior and posterior segment.
• accurately and punctually characterizing the morphological and pathophysiological elements peculiar to individual chorio-retinal diseases and identify new clinical biomarkers, also through screening programs and through the use of artificial intelligence systems.

In the field of neurophysiology of vision and neurophthalmology, the most significant products in reference to the objectives of the line are shown below:

• Objective 1: Through the definition of post-retinal dysfunction in glaucoma (see Parisi et al Front. Aging 2021; 13:697425) it is possible to make differential diagnoses between glaucoma and other pathologies that affect the optic nerve (e.g. meningions or other compressive lesions) with a specific classification and consequent neuroprotection or neuroenhancement therapeutic approach as reported in the review by Oddone et al. Pharmaceuticals (Basel). 2021; 14:281). The work carried out in patients with ataxia is of particular translational interest (see Ziccardi et al J. Clin. Med. 2021; 12, 10:5271) or with Multiple Sclerosis (see Parisi et al J Clin Med 2023;12:7175) in which it is possible to identify a neurodegenerative macular functional impairment by distinguishing it from the diagnostic point of view from other forms of maculopathy (e.g. myopic, age-related, hereditary), resulting in a different therapeutic approach.
• Objective 2: Having identified a new ciliopathy in the broad field of inherited retinal dystrophies (see Ziccardi et al J Mol Sci 2022; 23:14656) is certainly an important step for the phenotype-genotype definition of this pathology with the possibility of hypothesizing future specific gene therapies.

Objective 3: the evidence reported in the work carried out through specific neuro-imaging analyses (see Coppola et al J Headache Pain 2021; 22: 58 (2021) and Abagnale et al Front. Hum. Neurosci. 2023; 17: 1146302) have a double translational aspect: on the one hand, to provide a contribution to the knowledge of the neurophysiological mechanisms that determine the visual aura (with consequent limitation of the normal acts of daily life during migraine attacks) with possible future innovative therapeutic approaches (e.g. botulinum toxin type A and anti-CGRP monoclonal antibodies); on the other hand, to understand that specific structural abnormalities of the optical pathways are “characteristic” in migraine patients, laying the foundations for differential diagnoses with other degenerative brain diseases.