OVERVIEW

Contemporary medicine, following the sequencing of the human genome, has evolved into true "precision medicine". In ophthalmology, this means moving from simple clinical observation to understanding molecular mechanisms. This course aims to analyze how genetic variants and biochemical alterations transform the cornea from a transparent "biological crystal" into a pathological tissue, analyzing the functional defects underlying dystrophies and ectasias.

AIMS AND CONTENT

AIMS AND LEARNING OUTCOMES

The course provides advanced knowledge on mechanisms of protein misfolding, genetic alterations, and specific mutations affecting ocular tissues and the extracellular matrix, as well as oxidative stress processes. The goal is to enable the student to correlate a specific genetic mutation (Genotype) with the clinical and functional features of the pathology (Phenotype), laying the foundation for understanding modern gene therapies and selective surgical approaches.

At the end of the course, the student will be able to:

• Describe the molecular, genetic, and biochemical bases governing the architecture and transparency of ocular tissues.

• Correlate molecular alterations and protein misfolding with their corresponding clinical, dystrophic, and tissue decompensation presentations.

• Evaluate the structural and biomechanical defects underlying corneal and ocular motility disorders.

• Understand the clinical-molecular rationale of modern therapeutic frontiers, from gene therapy and editing to selective surgical and paratherapeutic techniques.

TEACHING METHODS

The teaching includes 8 hours of lectures.

N.B.: Students with valid certifications for Specific Learning Disorders (SLDs), disabilities or other educational needs are invited to contact the lecturer and the School/Department's disability referent at the beginning of the course to agree on possible teaching modalities that, while respecting the teaching objectives, take into account individual learning patterns.

SYLLABUS/CONTENT

Lecture 1: Molecular Architecture and Physics of Transparency

• From DNA structure to protein: How genes encode corneal order.

• Collagens (COL1A1, COL5A1): Genetic control of fibril diameter.

• Proteoglycans (KERA, LUM): The role of keratan sulfate and electrostatic repulsion.

• Physical Optics: The corneal lattice and constructive and destructive interference phenomena.

Lecture 2: Corneal Dystrophies – Synthesis Errors and Accumulation

• The CHST6 gene: Sulfation deficiency and loss of the interlamellar "safety distance".

• The TGFBI gene and Keratoepithelin: Misfolding mechanisms and toxic gain-of-function.

• Genotype-Phenotype Correlation: Analysis of mutational hotspots (R124 and R555).

• Deposit Biochemistry: Amyloid formation (Lattice Dystrophy) vs. hyaline deposits (Granular Dystrophy).

Lecture 3: Keratoconus – A Multifactorial and Biomechanical Pathology

• Beyond Mendelian genetics: Polygenicity and the role of epigenetics (microRNA).

• The LOX enzyme (Lysyl Oxidase): Deficiency of natural covalent cross-links between fibrils.

• Oxidative Stress and Inflammation: The role of reactive oxygen species (ROS) and Metalloproteinases (MMPs) as "molecular scissors".

• Interlamellar "Slipping": Molecular dynamics of corneal ectasia/bulging.

Lecture 4: Advanced Diagnostics and New Therapeutic Frontiers

• Biomolecular techniques: Genetic screening and early diagnosis of inherited diseases.

• Gene and Regenerative Therapy: Viral vectors and future approaches.

• Molecular rationale of Cross-linking (CXL): Creation of photo-induced artificial covalent bonds.

• Selective Surgery (DSAEK/DMEK): Treatment of endothelial decompensation (Fuchs Dystrophy) in light of tissue selectivity.

RECOMMENDED READING/BIBLIOGRAPHY

Reading items will be suggested or delivered by the teacher

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

March

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

Oral exam.

Registration for the exam is required: https://servizionline.unige.it/studenti/esami/

ASSESSMENT METHODS

The exam interview will focus on the topics covered in class: the student will have to demonstrate that he has understood the basic of biomolecular mechanisms and be able to expose what he has learned with awareness