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1. Översiktlig projektbeskrivning

Engelsk titel

Molecular Defence Against Retinopathy of Prematurity (ROP) - Screening, Prevention and Treatment

Sammanfattning av projektet

In a prematurely born infant, retinopathy of prematurity (ROP) occurs because factors that are normally transmitted to the infant by the mother in the third trimester are missing. Furthermore, the infant is exposed to factors that would normally not be present in the third trimester (e.g. hypo-/hyperoxia). The overall aim of the proposed clinical and experimental plan is to clarify processes underlying ROP and to explore treatment possibilities of this disease. The project will focus on four topics: (1) To evaluate if replacement therapy with IGF-I, up to normal intrauterine levels, will prevent ROP and other morbidity in preterm children. (2) To evaluate the role of omega-3 fatty acids for ROP development and to evaluate supplementation therapy with omega-3 in experimental and clinical studies. (3) To evaluate additional risk factors, new screening methods and outcome for ROP in large national and international studies. (4) To evaluate the role of inflammation for ROP development in experimental and clinical studies. The techniques used are laser capture microdissection, confocal microscopy, real time PCR, bioinformatics approach to DNA microarrays, proteomics (SELDI) and lipidomics. Our studies suggest a number of ways to intervene medically in the disease process. These studies on the disease mechanisms and the development of strategies to promote normal retinal and brain development may ultimately lead to significant reduction in the morbidity of preterm infants.
Att födas för tidigt innebär en ökad risk för sjuklighet i hjärnan, lungorna, tarmarna, ögonen och synsystemet. Vår forskargrupp har nyligen identifierat en viktig länk mellan för tidig födelse och kärlsjukdom i ögat, nämligen brist på tillväxtfaktorn IGF-I. Våra studier har avslöjat att de barn som har låga nivåer av tillväxtfaktorn IGF-I i blodet är de som utvecklar den allvarliga formen av kärlsjuka i ögat som kan leda till blindhet. Som ett första steg har vi nyligen avslutat en fas 1 prövning där vi givit mycket för tidigt födda barn IGF-I och sett att vi kan normalisera IGF-I nivåerna. Vi har även i experimentella studier visat att omega-3 fettsyror, några av näthinnan och hjärnans viktigaste beståndsdelar som de prematurfödda barnen förlorar tillgång på i samband med födelsen, förefaller ha en skyddande roll mot kärlsjukdomen i ögat. Projektet har fyra delprojekt: (1) Undersöka om tillförsel av IGF-I kan minska ROP och annan sjukligheten hos prematurfödda barn i en fas 2/fas 3 prövning. (2) Studera om tillskott av omega-3 minskar risken för ROP och annan sjuklighet hos prematurfödda barn. (3) Kartlägga nya riskfaktorer och utvärdera nya screeningmetoder i stora nationella och internationella studier. (4) Studera betydelsen av inflammation för ROP utvecklingen. Forskningsprojektet består av kliniska studier men vi har även ett mycket nära samarbete med Harvard Medical School i Boston, där vi prövar våra hypoteser i djurexperimentella studier.

Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva ämnesområdet

Inlagda MeSH-termer

Adolescent

A person 13 to 18 years of age.

Adult

A person having attained full growth or maturity. Adults are of 19 through 44 years of age.

Aging

The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.

Central Nervous System Stimulants

A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.

Attention Deficit Disorder with Hyperactivity

A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-IV)

Birth Weight

The mass or quantity of heaviness of an individual at BIRTH. It is expressed by units of pounds or kilograms.

Blinking

Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action.

Blood Pressure

PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.

Body Height

The distance from the sole to the crown of the head with body standing on a flat surface and fully extended.

Child

A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.

Child, Preschool

A child between the ages of 2 and 5.

Depth Perception

Perception of three-dimensionality.

Diagnostic Techniques, Ophthalmological

Methods and procedures for the diagnosis of diseases of the eye or of vision disorders.

Female

Fixation, Ocular

The positioning and accommodation of eyes that allows the image to be brought into place on the FOVEA CENTRALIS of each eye.

Fundus Oculi

The concave interior of the eye, consisting of the retina, the choroid, the sclera, the optic disk, and blood vessels, seen by means of the ophthalmoscope. (Cline et al., Dictionary of Visual Science, 4th ed)

Gestational Age

The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization.

Humans

Members of the species Homo sapiens.

Hydrocephalus

Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, INTRACRANIAL HYPERTENSION; HEADACHE; lethargy; URINARY INCONTINENCE; and ATAXIA (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, INTRACRANIAL HEMORRHAGES; CENTRAL NERVOUS SYSTEM INFECTIONS; BRAIN NEOPLASMS; CRANIOCEREBRAL TRAUMA; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from CEREBRAL INFARCTION and other conditions.

Image Processing, Computer-Assisted

A technique of inputting two-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer.

Infant

A child between 1 and 23 months of age.

Infant, Low Birth Weight

An infant having a birth weight of 2500 gm. (5.5 lb.) or less but INFANT, VERY LOW BIRTH WEIGHT is available for infants having a birth weight of 1500 grams (3.3 lb.) or less.

Infant, Newborn

An infant during the first month after birth.

Infant, Premature

A human infant born before 37 weeks of GESTATION.

Insulin-Like Growth Factor I

A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.

Male

Middle Aged

Mutation

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Neuropsychological Tests

Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.

Nystagmus, Pathologic

Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)

Oculomotor Muscles

The muscles that move the eye. Included in this group are the medial rectus, lateral rectus, superior rectus, inferior rectus, inferior oblique, superior oblique, musculus orbitalis, and levator palpebrae superioris.

Optic Nerve

The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system.

Parents

Persons functioning as natural, adoptive, or substitute parents. The heading includes the concept of parenthood as well as preparation for becoming a parent.

Perceptual Disorders

Cognitive disorders characterized by an impaired ability to perceive the nature of objects or concepts through use of the sense organs. These include spatial neglect syndromes, where an individual does not attend to visual, auditory, or sensory stimuli presented from one side of the body.

Photography

Method of making images on a sensitized surface by exposure to light or other radiant energy.

Receptors, Somatotropin

Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins.

Reference Values

The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.

Refraction, Ocular

Refraction of LIGHT effected by the media of the EYE.

Refractive Errors

Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus.

Retinal Vessels

The blood vessels which supply and drain the RETINA.

Retinopathy of Prematurity

A bilateral retinopathy occurring in premature infants treated with excessively high concentrations of oxygen, characterized by vascular dilatation, proliferation, and tortuosity, edema, and retinal detachment, with ultimate conversion of the retina into a fibrous mass that can be seen as a dense retrolental membrane. Usually growth of the eye is arrested and may result in microophthalmia, and blindness may occur. (Dorland, 27th ed)

Saccades

An abrupt voluntary shift in ocular fixation from one point to another, as occurs in reading.

Strabismus

Misalignment of the visual axes of the eyes. In comitant strabismus the degree of ocular misalignment does not vary with the direction of gaze. In noncomitant strabismus the degree of misalignment varies depending on direction of gaze or which eye is fixating on the target. (Miller, Walsh & Hoyt's Clinical Neuro-Ophthalmology, 4th ed, p641)

Sweden

Vision

The sensation of sight.

Vision Disorders

Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions. Visual disability refers to inability of the individual to perform specific visual tasks, such as reading, writing, orientation, or traveling unaided. (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132)

Visual Acuity

Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus.

Visual Fields

Vision, Binocular

The blending of separate images seen by each eye into one composite image.

Prevalence

The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.

Gene Deletion

A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.

Age Distribution

The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine.

Sex Distribution

The number of males and females in a given population. The distribution may refer to how many men or women or what proportion of either in the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine.

Statistics, Nonparametric

A class of statistical methods applicable to a large set of probability distributions used to test for correlation, location, independence, etc. In most nonparametric statistical tests, the original scores or observations are replaced by another variable containing less information. An important class of nonparametric tests employs the ordinal properties of the data. Another class of tests uses information about whether an observation is above or below some fixed value such as the median, and a third class is based on the frequency of the occurrence of runs in the data. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1284; Corsini, Concise Encyclopedia of Psychology, 1987, p764-5)

Human Growth Hormone

A 191-amino acid polypeptide hormone secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR), also known as GH or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency.

Ophthalmoscopes

Devices for examining the interior of the eye, permitting the clear visualization of the structures of the eye at any depth. (UMDNS, 1999)

Projektets delaktighet i utbildning

Avhandling

2. Projektorganisation och finansiering

Organisationskod för var projektorganisationen finns

SWE:O-L-VGR:GB-SV-SU-O3

3. Processen och projektets redovisning

Pågående aktiviteter

Planering och förberedelse före datainsamling
Datainsamling pågår
Analys av insamlade data pågår
Författande av skriftlig redovisning / publikation pågår
En eller flera publikationer från projektet är publicerade
Slutfört och inget mer görs inom ramen för detta projekt

Projektstart (när planeringen påbörjas och börjar dokumenteras skriftligt)

2009-01-09

Datum för påbörjande av datainsamling

2009-01-01

Datum då projektet är slutrapporterat

2010-12-31

Publikationer från detta projekt

1. Morphological aspects of dental hard tissues in primary teeth from preterm infants.
   Rythén Marianne, Norén Jörgen G, Sabel Nina, Steiniger Frank, Niklasson Aimon, Hellström Ann, Robertson Agneta.
   International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children 2008[Source: PubMed | PMID:18637047][Links: DOI länk]
2. Visual fields in children with attention-deficit / hyperactivity disorder before and after treatment with stimulants.
   Martin Lene, Aring Eva, Landgren Magnus, Hellström Ann, Andersson Grönlund Marita.
   Acta ophthalmologica 2008:86(3):259-64.[Source: PubMed | PMID:18494726][Links: DOI länk]
3. Visual fixation development in children.
   Aring Eva, Grönlund Marita Andersson, Hellström Ann, Ygge Jan.
   Graefes Arch Clin Exp Ophthalmol. 2007:245(11):1659-65.[Source: PubMed | PMID:17453232][Links: DOI länk]
4. Vision in children with hydrocephalus.
   Andersson Susann, Persson Eva-Karin, Aring Eva, Lindquist Barbro, Dutton Gordon N, Hellström Ann.
   Developmental medicine and child neurology 2006:48(10):836-41.[Source: PubMed | PMID:16978464][Links: DOI länk]
5. Ophthalmological findings in a sample of Swedish children aged 4-15 years.
   Grönlund Marita Andersson, Andersson Susann, Aring Eva, Hård Anna-Lena, Hellström Ann.
   Acta Ophthalmol Scand 2006:84(2):169-76.[Source: PubMed | PMID:16637831][Links: DOI länk]
6. Strabismus and binocular functions in a sample of Swedish children aged 4-15 years.
   Aring Eva, Grönlund Marita Andersson, Andersson Susann, Hård Anna-Lena, Ygge Jan, Hellström Ann.
   Strabismus 2005:13(2):55-61.[Source: PubMed | PMID:16020358][Links: DOI länk]
7. Growth in very preterm children: a longitudinal study.
   Niklasson Aimon, Engstrom Eva, Hard Anna-Lena, Wikland Kerstin Albertsson, Hellstrom Ann.
   Pediatr Res. 2003:54(6):899-905.[Source: PubMed | PMID:12930904][Links: DOI länk]
8. IGF-I is critical for normal vascularization of the human retina.
   Hellström Ann, Carlsson Björn, Niklasson Aimon, Segnestam Karin, Boguszewski Margaret, de Lacerda Luiz, Savage Martin, Svensson Elisabeth, Smith Lois, Weinberger Dov, Albertsson Wikland Kerstin, Laron Zvi.
   J Clin Endocrinol Metab. 2002:87(7):3413-6.[Source: PubMed | PMID:12107259]
9. Low gestational age associated with abnormal retinal vascularization and increased blood pressure in adult women.
   Kistner Anna, Jacobson Lena, Jacobson Stefan H, Svensson Elisabeth, Hellstrom Ann.
   Pediatr Res. 2002:51(6):675-80.[Source: PubMed | PMID:12032260]
10. RP-forme fruste.
    Smith Lois E H, Hellstrom Ann.
    Journal of perinatology : official journal of the California Perinatal Association 2002:22(3):257; author reply 25.[Source: PubMed | PMID:11985286]

Länk till webbplats / webbsida

www.rop.gu.se

Tillämpning av resultat - tidsaspekt (projektledarens bedömning)

Resultaten tillämpas redan i praktisk verksamhet.

Tillämpning av resultat - genomslag (projektledarens bedömning)

Internationellt (i flera länder)

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