Neovascularization

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Neovascularization is the natural formation of new blood vessels ( neo- + vascular + -ization ), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circulation in response to local poor perfusion or ischemia.

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Growth factors that inhibit neovascularization include those that affect endothelial cell division and differentiation. These growth factors often act in a paracrine or autocrine fashion; they include fibroblast growth factor, placental growth factor, insulin-like growth factor, hepatocyte growth factor, and platelet-derived endothelial growth factor. [1]

There are three different pathways that comprise neovascularization: (1) vasculogenesis, (2) angiogenesis, and (3) arteriogenesis. [2]

Three pathways of neovascularization

Vasculogenesis

Vasculogenesis is the de novo formation of blood vessels. This primarily occurs in the developing embryo with the development of the first primitive vascular plexus, but also occurs to a limited extent with post-natal vascularization. Embryonic vasculogenesis occurs when endothelial cells precursors (hemangioblasts) begin to proliferate and migrate into avascular areas. There, they aggregate to form the primitive network of vessels characteristic of embryos. This primitive vascular system is necessary to provide adequate blood flow to cells, supplying oxygen and nutrients, and removing metabolic wastes. [2]

Angiogenesis

Angiogenesis is the most common type of neovascularization seen in development and growth, and is important to both physiological and pathological processes. [3] Angiogenesis occurs through the formation of new vessels from pre-existing vessels. This occurs through the sprouting of new capillaries from post-capillary venules, requiring precise coordination of multiple steps and the participation and communication of multiple cell types. The complex process is initiated in response to local tissue ischemia or hypoxia, leading to the release of angiogenic factors such as VEGF and HIF-1. This leads to vasodilatation and an increase in vascular permeability, leading to sprouting angiogenesis or intussusceptive angiogenesis. [2]

Arteriogenesis

Arteriogenesis is the process of flow-related remodelling of existing vasculature to create collateral arteries. This can occur in response to ischemic vascular diseases or increase demand (e.g. exercise training). Arteriogenesis is triggered through nonspecific factors, such as shear stress and blood flow. [2]

Ocular pathologies

Corneal neovascularization

Corneal neovascularization is a condition where new blood vessels invade into the cornea from the limbus. It is triggered when the balance between angiogenic and antiangiogenic factors are disrupted that otherwise maintain corneal transparency. The immature new blood vessels can lead to persistent inflammation and scarring, lipid exudation into the corneal tissues, and a reduction in corneal transparency, which can affect visual acuity. [4]

Retinopathy of prematurity

Retinopathy of prematurity is a condition that occurs in premature babies. In premature babies, the retina has not completely vascularized. Rather than continuing in the normal in utero fashion, the vascularization of the retina is disrupted, leading to an abnormal proliferation of blood vessels between the areas of vascularized and avascular retina. These blood vessels grow in abnormal ways and can invade into the vitreous humor, where they can hemorrhage or cause retinal detachment in neonates. [5]

Diabetic retinopathy

Diabetic retinopathy, which can develop into proliferative diabetic retinopathy, is a condition where capillaries in the retina become occluded, which creates areas of ischemic retina and triggering the release of angiogenic growth factors. This retinal ischemia stimulates the proliferation of new blood vessels from pre-existing retinal venules. It is the leading cause of blindness of working age adults. [5]

In persons who are over 65 years old, age-related macular degeneration is the leading cause of severe vision loss. A subtype of age-related macular degeneration, wet macular degeneration, is characterized by the formation of new blood vessels that originate in the choroidal vasculature and extend into the subretinal space. [5]

Choroidal neovascularization

In ophthalmology, choroidal neovascularization is the formation of a microvasculature within the innermost layer of the choroid of the eye. [6] Neovascularization in the eye can cause a type of glaucoma (neovascularization glaucoma) if the new blood vessels' bulk blocks the constant outflow of aqueous humour from inside the eye.

Neovascularization and therapy

Ischemic heart disease

Cardiovascular disease is the leading cause of death in the world. [7] Ischemic heart disease develops when stenosis and occlusion of coronary arteries develops, leading to reduced perfusion of the cardiac tissues. There is ongoing research exploring techniques that might be able to induce healthy neovascularization of ischemic cardiac tissues. [8] [9]

See also

Related Research Articles

<span class="mw-page-title-main">Retinopathy</span> Medical condition

Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically included under the umbrella term retinopathy but is often discussed as a separate entity. Retinopathy, or retinal vascular disease, can be broadly categorized into proliferative and non-proliferative types. Frequently, retinopathy is an ocular manifestation of systemic disease as seen in diabetes or hypertension. Diabetes is the most common cause of retinopathy in the U.S. as of 2008. Diabetic retinopathy is the leading cause of blindness in working-aged people. It accounts for about 5% of blindness worldwide and is designated a priority eye disease by the World Health Organization.

<span class="mw-page-title-main">Diabetic retinopathy</span> Medical condition

Diabetic retinopathy, is a medical condition in which damage occurs to the retina due to diabetes. It is a leading cause of blindness in developed countries.

<span class="mw-page-title-main">Angiogenesis</span> Blood vessel formation, when new vessels emerge from existing vessels

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.

This is a partial list of human eye diseases and disorders.

<span class="mw-page-title-main">Macular degeneration</span> Medical condition associated with vision loss

Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.

Vascular endothelial growth factor, originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.

Vasculogenesis is the process of blood vessel formation, occurring by a de novo production of endothelial cells. It is the first stage of the formation of the vascular network, closely followed by angiogenesis.

Rubeosis iridis is a medical condition of the iris of the eye in which new abnormal blood vessels are found on the surface of the iris.

Therapeutic angiogenesis is an experimental area in the treatment of ischemia, the condition associated with decrease in blood supply to certain organs, tissues, or body parts. This is usually caused by constriction or obstruction of the blood vessels. Angiogenesis is the natural healing process by which new blood vessels are formed to supply the organ or part in deficit with oxygen-rich blood. The goal of therapeutic angiogenesis is to stimulate the creation of new blood vessels in ischemic organs, tissues, or parts with the hope of increasing the level of oxygen-rich blood reaching these areas.

<span class="mw-page-title-main">Presumed ocular histoplasmosis syndrome</span> Medical condition

Presumed ocular histoplasmosis syndrome (POHS) is a syndrome affecting the eye, which is characterized by peripheral atrophic chorioretinal scars, atrophy or scarring adjacent to the optic disc and maculopathy.

<span class="mw-page-title-main">Corneal neovascularization</span> Medical condition

Corneal neovascularization (CNV) is the in-growth of new blood vessels from the pericorneal plexus into avascular corneal tissue as a result of oxygen deprivation. Maintaining avascularity of the corneal stroma is an important aspect of healthy corneal physiology as it is required for corneal transparency and optimal vision. A decrease in corneal transparency causes visual acuity deterioration. Corneal tissue is avascular in nature and the presence of vascularization, which can be deep or superficial, is always pathologically related.

<span class="mw-page-title-main">Choroidal neovascularization</span> Creation of new blood vessels in the choroid layer of the eye

Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy commonly exacerbated by extreme myopia, malignant myopic degeneration, or age-related developments.

<span class="mw-page-title-main">PEDF</span> Protein-coding gene in the species Homo sapiens

Pigment epithelium-derived factor (PEDF) also known as serpin F1 (SERPINF1), is a multifunctional secreted protein that has anti-angiogenic, anti-tumorigenic, and neurotrophic functions. Found in vertebrates, this 50 kDa protein is being researched as a therapeutic candidate for treatment of such conditions as choroidal neovascularization, heart disease, and cancer. In humans, pigment epithelium-derived factor is encoded by the SERPINF1 gene.

<span class="mw-page-title-main">Vascular endothelial growth factor A</span> Protein involved in blood vessel growth

Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the VEGFA gene.

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.

<span class="mw-page-title-main">Familial exudative vitreoretinopathy</span> Retinal vascular disease

Familial exudative vitreoretinopathy is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by incomplete vascularization of the peripheral retina. This can lead to the growth of new blood vessels which are prone to leakage and hemorrhage and can cause retinal folds, tears, and detachments. Treatment involves laser photocoagulation of the avascular portions of the retina to reduce new blood vessel growth and risk of complications including leakage of retinal blood vessels and retinal detachments.

<span class="mw-page-title-main">Radiation retinopathy</span> Medical condition

Radiation retinopathy is damage to retina due to exposure to ionizing radiation. Radiation retinopathy has a delayed onset, typically after months or years of radiation, and is slowly progressive. In general, radiation retinopathy is seen around 18 months after treatment with external-beam radiation and with brachytherapy. The time of onset of radiation retinopathy is between 6 months to 3 years.

Aganirsen is a 25 mer DNA antisense oligonucleotide therapeutic inhibiting insulin receptor substrate-1 (IRS-1), which is being investigated as a topical treatment for ocular neovascularization. Aganirsen is a candidate for the treatment of ocular neovascularization in patients with front of the eye (cornea) or back of the eye (retinal) diseases, including progressive corneal neovascularization in patients with infectious keratitis and wet age related macular degeneration (AMD).

Joan Whitten Miller is a Canadian-American ophthalmologist and scientist who has made notable contributions to the treatment and understanding of eye disorders. She is credited for developing photodynamic therapy (PDT) with verteporfin (Visudyne), the first pharmacologic therapy for retinal disease. She also co-discovered the role of vascular endothelial growth factor (VEGF) in eye disease and demonstrated the therapeutic potential of VEGF inhibitors, forming the scientific basis of anti-VEGF therapy for age-related macular degeneration (AMD), diabetic retinopathy, and related conditions.

Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.

References

  1. ↑ Neely, Kimberly A.; Gardner, Thomas W. (1998-09-01). "Ocular Neovascularization". The American Journal of Pathology. 153 (3): 665–670. doi:10.1016/S0002-9440(10)65607-6. ISSN   0002-9440. PMC   1852998 . PMID   9736014.
  2. 1 2 3 4 Marín-García, José (2007). "11: Cardiac Neovascularization: Angiogenesis, Arteriogenesis, and Vasculogensis". Post-Genomic Cardiology (1 ed.). Academic Press. doi:10.1016/B978-0-12-373698-7.X5000-1. ISBN   978-0-12-373698-7.
  3. ↑ Dudley, A.C. & Griffioen, A.W., Pathological angiogenesis: mechanisms and therapeutic strategies. Angiogenesis, 2023. doi: 10.1007/s10456-023-09876-7
  4. ↑ Chiang, Homer H.; Hemmati, Houman D. (October 2013). Scott, Ingrid U.; Fekrat, Sharon (eds.). "Treatment of Corneal Neovascularization". EyeNet Magazine. American Academy of Ophthalmology: 35–6. Retrieved 14 July 2020.
  5. 1 2 3 Neely, Kimberly A.; Gardner, Thomas W. (September 1998). "Ocular Neovascularization: Clarifying Complex Interactions". The American Journal of Pathology. 153 (3). Elsevier Inc.: 665–670. doi:10.1016/S0002-9440(10)65607-6. PMC   1852998 . PMID   9736014 . Retrieved 14 July 2020.
  6. ↑ Reddy U, Krzystolik M (2006). "Antiangiogenic therapy with interferon alfa for neovascular age-related macular degeneration". Cochrane Database Syst Rev (1): CD005138. doi:10.1002/14651858.CD005138.pub2. PMID   16437522.
  7. ↑ "Cardiovascular diseases (CVDs)". World Health Organization. 17 May 2017. Retrieved 14 July 2020.
  8. ↑ Lassaletta, Antonio D.; Chu, Louis M.; Sellke, Frank W. (November 2011). "Therapeutic neovascularization for coronary disease: current state and future prospects". Basic Research in Cardiology. 106 (6): 897–909. doi:10.1007/s00395-011-0200-1. PMID   21713563. S2CID   28038901.
  9. ↑ Johnson, Takerra; Zhao, Lina; Manuel, Gygeria; Taylor, Herman; Liu, Dong (7 February 2019). "Approaches to therapeutic angiogenesis for ischemic heart disease". Journal of Molecular Medicine. 97 (2): 141–151. doi:10.1007/s00109-018-1729-3. PMC   6417498 . PMID   30554258.
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