A Single Drop in the Eye – Effects on the Whole Body

Peer reviewe

Expression and function of angiotensins in the regulation of intraocular pressure : an experimental study

Glaucoma is a multifactorial long-term ocular neuropathy associated with progressive loss of the visual field, retinal nerve fiber structural abnormalities and optic disc changes. Like arterial hypertension it is usually a symptomless disease, but if left untreated leads to visual disability and eventual blindness. All therapies currently used aim to lower intraocular pressure (IOP) in order to minimize cell death. Drugs with new mechanisms of action could protect glaucomatous eyes against blindness. Renin-angiotensin system (RAS) is known to regulate systemic blood pressure and compounds acting on it are in wide clinical use in the treatment of hypertension and heart failure but not yet in ophthalmological use. There are only few previous studies concerning intraocular RAS, though evidence is accumulating that drugs antagonizing RAS can also lower IOP, the only treatable risk factor in glaucoma. The main aim of this experimental study was to clarify the expression of the renin-angiotensin system in the eye tissues and to test its potential oculohypotensive effects and mechanisms. In addition, the possible relationship between the development of hypertension and IOP was evaluated in animal models. In conclusion, a novel angiotensin receptor type (Mas), as well as ACE2 enzyme- producing agonists for Mas, were described for the first time in the eye structures participating in the regulation of IOP. In addition, a Mas receptor agonist significantly reduced even normal IOP. The effect was abolished by a specific receptor antagonist. Intraocular, local RAS would thus to be involved in the regulation of IOP, probably even more in pathological conditions such as glaucoma though there was no unambiguous relationship between arterial and ocular hypertension. The findings suggest the potential as antiglaucomatous drugs of agents which increase ACE2 activity and the formation of angiotensin (1-7), or activate Mas receptors.Tutkimuksen tavoitteena oli selvittää kokeellisesti reniini-angiotensiinijärjestelmän (RAS) esiintymistä silmässä, sen eri osatekijöiden mahdollista silmänpainetta alentavaa vaikutusta sekä silmänpaineen alenemisen mekanismia ja yhteyttä verenpaineeseen. RAS järjestelmän tiedetään osallistuvan keskeisesti verenpaineen säätelyyn, ja siihen vaikuttavat yhdisteet ovat laajassa kliinisessä käytössä verenpainetaudin ja sydämen vajaatoiminnan hoidossa. Silmänpainetaudin eli glaukooman hoidossa tämä lääkeaineryhmä ei vielä ole käytössä, ja aikaisempaa tutkimustietoa on vähän. Tutkimuksessa saatiin uutta tietoa tietoa aktiivisesta silmänsisäisestä RAS järjestelmästä. Merkittävimmät löydökset olivat uuden reseptorityypin (Mas) löytyminen silmäkudoksesta sekä sitä kautta vaikuttavan aktiivisen entsyymin (ACE2) esiintyminen silmänpaineen muodostumisen kannalta oleellisista silmän rakenteista. Mas reseptoria aktivoivalla yhdisteellä saatiin silmänsisäinen paine laskemaan normaalipaineisessa silmässä. Painetta alentava vaikutus oli kumottavissa saman reseptorityypin salpauksella. Alustavien kokeiden perusteella vaikutus oli huomattava korkeapaineisessa silmässä. Yksiselitteistä yhteyttä koholla olevan verenpaineen ja silmänpaineen välille ei saatu Glaukooma on verenpainetaudin tavoin pitkään lähes oireeton sairaus, jonka perimmäinen syy on vielä tuntematon. Hoitamattomana se johtaa hermosäiekatoon, näkökenttäpuutoksiin ja lopulta sokeutumiseen. Silmänpaineen tiedetään olevan ainoa hoidettavissa oleva riskitekijä, jota alentamalla voidaan estää tai pysäyttää peruuttamaton näköhermovaurio. Sairauden päätyyppiä hoidetaan ensisijaisesti silmän pinnalle annosteltavilla paikallislääkkeillä. Tähänastiset glaukooman hoidossa käytettävät lääkkeet kuuluvat joko kolinergisen tai adrenergisen järjestelmän yhdisteisiin, hiilihappoanhydraasin estäjiin tai prostaglandinianalogeihin. Niiden tarkka vaikutusmekanismi on tuntematon, mutta ne joko vähentävät kammionesteen tuottoa tai lisäävät sen poistumista, joiden välisestä tasapainosta silmän sisäinen paine muodostuu. Silmänpainetaudin vuoksi ylemmän ryhmän erityiskorvattaviin lääkkeisiin oikeutettuja on Suomessa noin 72 000 potilasta. Sairaus yleistyy iän myötä, ja sen määrä on jatkuvassa kasvussa. Uuden lääkeaineryhmän löytyminen saattaisi ehkäistä aikaisempaa tehokkaammin pysyvän näkökenttävaurion kehittymistä ja sokeutumista. Suuren haasteen lääkekehittelylle tulee antamaan aktiivisten aineiden saattaminen silmän sisään

Local ocular renin-angiotensin-aldosterone system : any connection with intraocular pressure? A comprehensive review

The renin-angiotensin system (RAS) is one of the oldest and most extensively studied human peptide cascades, well-known for its role in regulating blood pressure. When aldosterone is included, RAAS is involved also in fluid and electrolyte homeostasis. There are two main axes of RAAS: (1) Angiotensin (1-7), angiotensin converting enzyme 2 and Mas receptor (ACE2-Ang(1-7)-MasR), (2) Angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor (ACE1-AngII-AT1R). In its entirety, RAAS comprises dozens of angiotensin peptides, peptidases and seven receptors. The first mentioned axis is known to counterbalance the deleterious effects of the latter axis. In addition to the systemic RAAS, tissue-specific regulatory systems have been described in various organs, evidence that RAAS is both an endocrine and an autocrine system. These local regulatory systems, such as the one present in the vascular endothelium, are responsible for long-term regional changes. A local RAAS and its components have been detected in many structures of the human eye. This review focuses on the local ocular RAAS in the anterior part of the eye, its possible role in aqueous humour dynamics and intraocular pressure as well as RAAS as a potential target for anti-glaucomatous drugs.KEY MESSAGES Components of renin-angiotensin-aldosterone system have been detected in different structures of the human eye, introducing the concept of a local intraocular renin-angiotensin-aldosterone system (RAAS). Evidence is accumulating that the local ocular RAAS is involved in aqueous humour dynamics, regulation of intraocular pressure, neuroprotection and ocular pathology making components of RAAS attractive candidates when developing new effective ways to treat glaucoma.Peer reviewe

Many faces of renin-angiotensin system - focus on eye

Peer reviewe

Changes in incidence and severity of visual impairment due to glaucoma during 40 years – a register-based study in Finland

Publisher Copyright: © 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.Purpose: To report the incidence and severity of reported visual impairment (VI) due to glaucoma and the changes in them during the past 40 years in Finland. Methods: A register-based study, in which the data were collected from the Finnish Register of Visual Impairment between 1980 and 2019. These data included 5819 visually impaired glaucoma patients, of which 61% were female. Visual impairment (VI) was classified according to the Finnish national definitions. The number of treated glaucoma patients in Finland was calculated using glaucoma medication reimbursement data available between 1986 and 2019 from the Social Insurance Institution of Finland registers. Results: The incidence of reported VI due to glaucoma per 100 000 persons had increased from 2.3 in the 1980s to 3.4 in the 2010s. During the same time period, the incidence of reported VI per 10 000 treated glaucoma patients had decreased from 32 in the 1980s to 21 in the 2010s. Primary open-angle glaucoma (45%) was the main subtype for reported VI due to glaucoma. During the 40 years, the proportion of mild VI and the age at the onset of reported VI had increased. Conclusion: The incidence of reported VI due to glaucoma has increased during the 40 years, but the risk of treated glaucoma patients becoming visually impaired has decreased. Visual impairment (VI) also occurs at an older age. This is likely due to the earlier diagnoses and improved therapy. To prevent the unfavourable development of VI due to glaucoma among the ageing population in the future, all attempts need to be made to improve glaucoma care.Peer reviewe

Glaucoma progression in patients receiving intravitreal anti-VEGF treatment for neovascular age-related macular degeneration

Purpose: The purpose of this study was to investigate how often glaucoma and neovascular age-related macular degeneration (nAMD) occur in the same patient and to evaluate whether glaucoma progression is faster in eyes treated with intravitreal anti-VEGF medications for nAMD. Methods: This single-centre retrospective real-world data (RWD) consists of medical records of 6314 glaucoma and 2166 nAMD patients treated in 2008–2017 in Tays Eye Centre, Finland. To study glaucoma progression, changes in visual fields (mean deviation [MD], dB/year), IOP (mmHg/year) and fundus photographs (progression, yes/no) were compared in glaucoma eyes with and without anti-VEGF treatment for nAMD and ≥1 year follow-up. Results: During the 10-year period, 147 patients with glaucoma received intravitreal anti-VEGF treatment for nAMD corresponding to 2% of glaucoma and 7% of nAMD patients. The mean change in MD was −0.70 dB/year (SD 1.8) vs. −0.27 dB/year (SD 1.7) (p = 0.027) in glaucoma eyes with (n = 37) and without (n = 4304) anti-VEGF injections, respectively. In patients with bilateral glaucoma and unilateral nAMD treated with anti-VEGF injections (n = 20), MD declined at −0.62 dB/year (SD 1.9) vs 0.33 dB/year (SD 1.5) (p = 0.654), and glaucoma progression was detected in 14/20 vs 10/20 (p = 0.219) fundus photographs in eyes with anti-VEGF treatment compared with their untreated fellow eyes. Conclusion: nAMD and glaucoma were found co-existing in the same eye at rates that were similar to the age-corrected prevalence of the two diseases in the general population. Our results suggest that intravitreal anti-VEGF treatment for nAMD may accelerate glaucoma progression.publishedVersionPeer reviewe

Age-associated changes in human tear proteome

Additional file 1. Analysis results of proteins with unadjusted p-value < 0.05

Immediate sequential bilateral cataract surgery : A 13-year real-life report of 56 700 cataract operations

Background/aims: To assess the frequency of immediate sequential bilateral cataract surgery (ISBCS) and endophthalmitis during 13-year period in Tays Eye Centre, Tampere University Hospital, Tampere, Finland. Methods: All cataract surgeries performed between 1 January 2008 and 31 December 2020, and all endophthalmitis cases during the same period were searched from electronic patient records. Numbers and frequencies of ISBCS, and complications, including endophthalmitis and vitreous loss, were recorded and compared with unilateral operations. Results: The study included 56 700 cataract surgeries in 34 797 patients of whom 39% (n=13 445) had ISBCS. The median age of the patients was 75 (IQR 68-80, range 0.08-99) years at the time of surgery. The proportion of ISBCS patients increased from 4.2% in 2008 to 46% in 2020. Vitreous loss occurred in 480 (0.9%) of cataract surgeries. There were no postoperative endophthalmitis after cataract surgery (n=0) during the 13-year period. Conclusion: The proportion of patients undergoing ISBCS increased from 4.2% in 2008 to 46% in 2020. No endophthalmitis were found to be associated with ISBCS.publishedVersionPeer reviewe

Vaikeahoitoinen epilepsia.

Syventävä työ ei kirjastoss

Vaikeahoitoinen epilepsia.

Syventävä työ ei kirjastoss