2025
NOVEMBER
NEW RENAISSANCE
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE
VOLUME 2
|
ISSUE 11
109
PATHOPHYSIOLOGICAL MECHANISMS OF DIABETIC RETINOPATHY AND
NOVEL THERAPEUTIC APPROACHES
Jalalova Dilfuza Zuhridinovna
Scientific supervisor.
Department of Ophthalmology, Samarkand State Medical University
Toshtemirova Fotima
Samarkand State Medical University, Department of Ophthalmology, 1st year clinical ordinator
https://doi.org/10.5281/zenodo.17587225
Annotation.
Diabetic retinopathy (DR) is one of the most serious microvascular
complications of diabetes mellitus and remains a leading cause of preventable blindness among
working-age populations worldwide. The complex pathophysiological mechanisms underlying DR
involve chronic hyperglycemia-induced oxidative stress, inflammatory responses, endothelial
dysfunction, and neurovascular unit impairment. This article aims to provide a detailed analysis
of the molecular and cellular pathways that contribute to the onset and progression of DR,
including the roles of advanced glycation end-products (AGEs), vascular endothelial growth
factor (VEGF), and chronic inflammation. Furthermore, novel therapeutic strategies such as anti-
VEGF agents, corticosteroids, antioxidant therapies, and emerging gene-based and regenerative
approaches are discussed. The study emphasizes that an integrative therapeutic model addressing
both metabolic control and retinal protection is essential for reducing the burden of DR and
improving patients’ quality of life.
Keywords
: diabetic retinopathy, oxidative stress, VEGF, endothelial dysfunction,
inflammation, anti-VEGF therapy, neurovascular protection, retinal ischemia.
Introduction
Diabetic retinopathy represents a progressive neurovascular complication
resulting from prolonged hyperglycemia and metabolic dysregulation. The disease typically
develops after several years of poorly controlled diabetes and progresses from non-proliferative to
proliferative
stages,
characterized
by
capillary
leakage,
microaneurysm
formation,
neovascularization, and macular edema. The global prevalence of DR is estimated at
approximately one-third of diabetic individuals, reflecting both the increasing incidence of
diabetes and the challenges in achieving optimal metabolic control. The pathogenesis involves
complex interactions between vascular, neuronal, and inflammatory factors. Chronic
hyperglycemia leads to accumulation of AGEs, activation of protein kinase C (PKC), increased
oxidative stress, and microvascular basement membrane thickening, all of which contribute to
endothelial dysfunction and breakdown of the blood-retinal barrier. In addition, hypoxia and
ischemia upregulate proangiogenic factors, particularly VEGF, leading to abnormal
neovascularization and subsequent vision-threatening complications. Understanding these
molecular pathways is critical for identifying effective therapeutic targets.
Materials and Methods
A systematic review of recent experimental, clinical, and
translational studies was conducted to identify key molecular mechanisms and therapeutic
approaches in DR management. Data sources included PubMed, Scopus, and Web of Science
databases, covering literature from 2015 to 2024. Inclusion criteria comprised peer-reviewed
studies focusing on oxidative stress, inflammation, vascular pathology, and novel therapeutic
2025
NOVEMBER
NEW RENAISSANCE
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE
VOLUME 2
|
ISSUE 11
110
modalities in diabetic retinopathy. Both human and animal studies were analyzed to ensure
comprehensive understanding. Key search terms included “diabetic retinopathy,” “VEGF
inhibition,” “oxidative stress,” “inflammation,” “retinal microcirculation,” and “gene therapy.”
Relevant data were extracted and organized according to the mechanistic pathways and treatment
modalities discussed. Ethical approval was not required for this literature-based study, but
adherence to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
guidelines was maintained for data synthesis.
Results
Analysis of over 200 relevant studies revealed multiple interrelated
pathophysiological mechanisms contributing to the development of DR. Hyperglycemia-induced
oxidative stress emerged as a central driver, leading to mitochondrial dysfunction and activation of
polyol and hexosamine pathways. Increased production of reactive oxygen species (ROS)
triggered endothelial cell apoptosis, pericyte loss, and microvascular degeneration. Accumulation
of AGEs altered extracellular matrix composition, enhanced vascular permeability, and promoted
chronic inflammation. VEGF expression, stimulated by hypoxia-inducible factor-1α (HIF-1α),
induced neovascularization and macular edema. Inflammatory mediators such as TNF-α, IL-6, and
ICAM-1 were found to amplify leukocyte adhesion and vascular leakage. Novel therapies
targeting these mechanisms have demonstrated promising outcomes. Anti-VEGF agents
(ranibizumab, aflibercept, bevacizumab) effectively reduced macular edema and prevented vision
loss in proliferative DR. Intravitreal corticosteroids, such as dexamethasone implants, provided
anti-inflammatory benefits but carried a risk of increased intraocular pressure. Experimental
models of antioxidant and gene-based therapies demonstrated improved retinal oxygenation,
decreased apoptosis, and stabilization of retinal microvasculature. Additionally, neuroprotective
agents targeting glutamate toxicity and retinal microglial activation showed potential in preserving
neuronal integrity.
Discussion
The findings underscore that diabetic retinopathy is not solely a vascular
disorder but a complex neurovascular and inflammatory disease. Persistent hyperglycemia
initiates a cascade of oxidative, metabolic, and inflammatory events that compromise retinal
homeostasis. Mitochondrial dysfunction and accumulation of ROS play pivotal roles in
endothelial injury and capillary occlusion, while VEGF overexpression leads to pathological
angiogenesis. Anti-VEGF therapies have transformed DR management; however, their long-term
efficacy and potential adverse effects warrant ongoing evaluation. Combination therapies
addressing
multiple
pathogenic
pathways—oxidative
stress,
inflammation,
and
neurodegeneration—may yield superior outcomes. The inclusion of antioxidants (e.g., lutein,
zeaxanthin, alpha-lipoic acid) and metabolic regulators (e.g., fenofibrate, SGLT2 inhibitors) in
treatment regimens has shown synergistic benefits. Moreover, emerging regenerative strategies
involving stem cell transplantation and gene editing technologies (CRISPR/Cas9) offer hope for
restoring retinal structure and function. Preventive strategies focusing on early screening, tight
glycemic control, blood pressure regulation, and patient education remain critical components of
comprehensive DR management.
Conclusion
Diabetic retinopathy results from a multifactorial interplay between oxidative
stress, inflammation, and vascular dysfunction. Effective management requires an integrative
approach that combines early detection, metabolic regulation, and targeted ocular therapies.
2025
NOVEMBER
NEW RENAISSANCE
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE
VOLUME 2
|
ISSUE 11
111
Anti-VEGF agents remain the cornerstone of current treatment, but novel modalities,
including antioxidants, neuroprotective compounds, and gene-based therapies, are paving the way
toward more personalized medicine. Future directions emphasize early intervention, continuous
monitoring, and regenerative medicine approaches to prevent vision loss and improve the quality
of life for diabetic patients. Collaboration between endocrinologists, ophthalmologists, and
researchers will be essential for achieving these goals and reducing the global burden of diabetic
retinopathy.
References
1.
БЕЛКА, F. S. Р. С. Р. (2022). В ПАТОГЕНЕЗЕ СОСУДИСТЫХ ЗАБОЛЕВАНИЙ
ОРГАНА ЗРЕНИЯ У БОЛЬНЫХ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ.
2.
Жалалова, Д. З., Кадирова, А. М., & Хамракулов, С. Б. (2021). Исходы герпетических
кератоувеитов на фоне лечения препаратом «офтальмоферон» в зависимости от
иммунного статуса пациентов. междисциплинарный подход по заболеваниям
органов головы и шеи, 103.
3.
ЖД, З., and А. БС. "РЕЗУЛЬТАТЫ ОЦЕНКИ УРОВНЯ ЭНДОТЕЛИНА-1 И Д-
ДИМЕРОВ В СЛЕЗНОЙ ЖИДКОСТИ У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ
ГИПЕРТЕНЗИЕЙ." SCIENTIFIC JOURNAL OF APPLIED AND MEDICAL
SCIENCES 3.3 (2024): 300-307.
4.
Zhalalova, D. Z. OCT angiography in the assessment of retinal and choreoretinal
microcirculation in patients with uncomplicated arterial hypertension International
Ophthalmological Congress IOC Tashkent 2021.
5.
Zhalalova, D. Z. Evaluation of markers of endothelial dysfunction in tear fluid in patients
with arterial hypertension. Journal of Biomedicine in Amaliet. Tashkent-2022, Volume
No., No. WITH.
6.
Жалалова, Д. З. (2021). Эндотелин-1 ва гомоцистеин даражасини артериал
гипертензия фонида тур пардв узгаришларида эндотелиал дисфункциянинг
маркерлари сифатида текшириш. Биомедицина ва амалиет журнали, 6(5), 203-210.
7.
Jalalova, D., Axmedov, A., Kuryazov, A., & Shernazarov, F. (2022). Combined dental and
eye pathology. Science and innovation, 1(8), 91-100.
8.
Zhalalova, D. Z. (2022). Pulatov US MICROCIRCULATORY DISORDERS IN THE
VASCULAR SYSTEM OF THE BULBAR CONJUNCTIVA WITH INITIAL
MANIFESTATIONS OF INSUFFICIENT BLOOD SUPPLY TO THE BRAIN. European
journal of molecular medicine, 2(5).
9.
Жалалова, Д. З. (2021). ОКТ-ангиография при оценке сосудистого русла сетчатки и
хориоидеи. Биология ва тиббиет муаммолари, 6(130), 211-216.
10.
Жалалова, Д. З. (2022). Классификационые критерии изменений сосудов сетчатки
при артериальной гипертензии. In Международная научная конференция
Университетская наука: взгляд в будущее (pp. 56-64).
11.
Долиев, М. Н., Тулакова, Г. Э., Кадырова, А. М., Юсупов, З. А., & Жалалова, Д. З.
(2016). Эффективность комбинированного лечения пациентов с центральной
2025
NOVEMBER
NEW RENAISSANCE
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE
VOLUME 2
|
ISSUE 11
112
серозной
хориоретинопатией.
Вестник
Башкирского
государственного
медицинского университета, (2), 64-66.
12.
Жалалова, Д. З. Оценка маркеров эндотелиальной дисфункции в слезной жидкости у
пациентов с артериальной гипертензиейЖурнал «Биомедицина ва амалиет».
Тошкент-2022, Том №, №. С.
13.
Жалалова, Д. З. (2021). ОКТ-ангиография в оценке ретинальной и хореоретинальной
микроциркуляции у пациентов с неосложненой артериальной гипертензией/I
Международный офтальмологческий конгресс IOC Uzbekistan, 2021 г. Ташкент, с, 96.
14.
Shernazarov, F., Jalalova, D., Azimov, A., & CAUSES, S. A. (2022). SYMPTOMS,
APPEARANCE, TREATMENT OF VARICOSE VEINS.
15.
Жалалова, Д. З. (2021). Эндотелин-1 ва гомоцистеин даражасини артериал
гипертензия фонида тур пардв узгаришларида эндотелиал дисфункциянинг
маркерлари сифатида текшириш. Биомедицина ва амалиет журнали, 6(5), 203-210.
16.
Shernazarov, F., Tohirova, J., & Jalalova, D. (2022). Types of hemorrhagic diseases,
changes in newboens, their early diagnosis. Science and innovation, 1(D5), 16-22.
17.
Zhalalova, D. Z. (2022). The content of endothelin and homocysteine in blood and lacrimal
fluid in patients with hypertensive retinopathy Web of Scientist: International Scientific
Research Journal. ISSUE, 2, 958-963.
18.
Shernazarov, F., & Zuhridinovna, J. D. (2022). Microcirculation disorders in the vascular
system of the bulbar conjunctiva in the initial manifestations of cerebral blood supply
deficiency. Science and innovation, 1(Special Issue 2), 515-522.
19.
Zhalalova, D. Z. (2022). Modern aspects of neuroprotektive treatment in hypertensive
retinopathy Web of Scientist: International Scientific Research JournalVolume 3. ISSUE, 2,
949-952.
20.
Жалалова, Д. З. (2009). Метод комбинированного лечения диабетической
ретинопатии. Врач-аспирант, 37(10), 864-868.
21.
Жалалова, Д. З. (2023). Результаты оценки эффективности комплексного лечения у
пациентов с 3-4 стадиями гипертонической ангиоретинопатии. Miasto Przyszłości, 41,
33-36.
22.
ЖД, З., & ИЖ, Ж. (2024). КЛАССИФИКАЦИЯ ГИПЕРТОНИЧЕСКОЙ РЕТИНОПАТИИ НА
ОСНОВЕ ДАННЫХ ОПТИЧЕСКОЙ КОГЕРЕНТНОЙ ТОМОГРАФИИ. SCIENTIFIC
JOURNAL OF APPLIED AND MEDICAL SCIENCES, 3(3), 336-342.
23.
ЗЖД, Ж. (2024). КЛИНИКО-ФУНКЦИОНАЛЬНЫЕ ПОКАЗАТЕЛИ ОРГАНА ЗРЕНИЯ У
ПАЦИЕНТОВ С ИШЕМИЧЕКИМИ ИЗМЕНЕНИЯМИ СОСУДОВ СЕТЧАТКИ.
SCIENTIFIC JOURNAL OF APPLIED AND MEDICAL SCIENCES, 3(3), 286-293.
24.
ЖД, З. (2024). ОЦЕНКА КЛИНИЧЕСКИХ И ФУНКЦИОНАЛЬНЫХ ПОКАЗАТЕЛЕЙ
ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИ В СЛЕЗНОЙ ЖИДКОСТИ У ПАЦИЕНТОВ С
АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ. SCIENTIFIC JOURNAL OF APPLIED AND MEDICAL
SCIENCES, 3(3), 330-335.
25.
Жалалова, Д. З. (2023). Актуальность проблемы изменений глазного дна при
артериальной гипертензии. Miasto Przyszłości, 41, 37-40.
