Overview of pharmacological treatments for presbyopia

Background: Presbyopia is the normal progressive waning of accommodation with loss of the visual ability to focus on objects residing at different distances. Presbyopia exacts a cost in quality of life and professional efficiency of many people over 40 years of age. Presbyopia is likely to be 1 of the main pressing visual concerns of the 21st century, given that life expectancy is increasing, resulting in an aging population. This review aimed to address the 3 strategies of the pharmacological treatment for presbyopia. Methods: A review on PubMed/MEDLINE, Google Scholar, and Clinicaltrials.gov was performed to investigate the English literature on pharmacological treatment for presbyopia from beginning-of-year 2012 to September 30, 2020. Results: In addition to the treatment of presbyopia with glasses or contact lenses, new surgical strategies have been developed, some of which have been successful. However, during the last decade, a new, promising, non-invasive option for treating presbyopia has emerged: the pharmacological approach. Many researchers have developed 3 different lines of investigation from different assumptions, on a pharmacological basis. The first consisted of producing miosis, to take advantage of a pharmacologically induced pinhole effect, increasing depth-of-focus, and thus improving uncorrected near visual acuity. The second aimed to rehabilitate accommodation binocularly to enable good vision at all distances. Finally, the third approach attempted to rehabilitate lost elasticity in the human crystalline lens. Conclusions: None of the 3 discussed pharmacological strategies for treating presbyopia, prescribed globally, but patients of restoring accommodation strategy can adhere locally, where they are sold so far as master prescriptions

Presbyopia: a New Potential Pharmacological Treatment

Presbyopia occurs after 40 years of age in humans with a progressive loss of accommodation. Accommodation depends on the contraction of the ciliary muscle and iris, lens changes and convergence.  The parasympathetic system regulates the degree of ciliary muscle and iris contraction necessary to modify the shape and position of the lens and its stimulation is effective through the activation of muscarinic receptors that are present in both structures. The hypothesis proposed here suggests the correction of accommodation in emmetropic presbyopic patients using a pharmacological treatment that includes a cholinergic agent combined with non-steroidal anti-inflammatory drugs (NSAIDs). This drug combination can restore near vision without affecting distance vision. It is important to note that the pharmaceutical form used was devoid of any inflammatory or other collateral effects

Presbyopia: a New Potential Pharmacological Treatment

Presbyopia occurs after 40 years of age in humans with a progressive loss of accommodation. Accommodation depends on the contraction of the ciliary muscle and iris, lens changes and convergence.  The parasympathetic system regulates the degree of ciliary muscle and iris contraction necessary to modify the shape and position of the lens and its stimulation is effective through the activation of muscarinic receptors that are present in both structures. The hypothesis proposed here suggests the correction of accommodation in emmetropic presbyopic patients using a pharmacological treatment that includes a cholinergic agent combined with non-steroidal anti-inflammatory drugs (NSAIDs). This drug combination can restore near vision without affecting distance vision. It is important to note that the pharmaceutical form used was devoid of any inflammatory or other collateral effects

Characterization of Tn6238 with a New Allele of aac(6′)-Ib-cr

Here, we report that the genetic structure of Tn1331 remained conserved in Argentina from 1989 to 2013 (72 of 73 isolates), with the exception being the plasmid-borne Tn1331-like transposon Tn6238 containing a new aac(6′)-Ib-cr allele recovered from a colistin-resistant Klebsiella pneumoniae clinical isolate. A bioinformatic analysis of aac(6′)-Ib-like gene cassettes suggests that this new aac(6′)-Ib-cr allele emerged through mutation or homologous recombination in the Tn1331 genetic platform. Tn6238 is a novel platform for the dissemination of aminoglycoside and fluoroquinolone resistance determinants.Fil: Quiroga, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Orman, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Errecalde, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Kaufman, Sara. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Centron, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Developmental Changes in Accommodation Evidenced by an Ultrabiomicroscopy Procedure in Patients of Different Ages

We demonstrate that changes in the behaviour of the contractile ciliary muscle accompanied by augmented rigidity of the lens are the most important aspects in the loss of accommodation. With ultrabiomicroscopy (UBM), we demonstrated that the performance of the ciliary muscle is diminished and accompanied by rigidity of the lens. Both lens thickness and trabecular-ciliary process distance (TCPD) were the parameters that showed major alterations with the loss of accommodation in patients of different ages. The results indicated that the differences between these parameters in farsightedness and nearsightedness in the different groups of patients were positively correlated

Developmental Changes in Accommodation Evidenced by an Ultrabiomicroscopy Procedure in Patients of Different Ages

We demonstrate that changes in the behaviour of the contractile ciliary muscle accompanied by augmented rigidity of the lens are the most important aspects in the loss of accommodation. With ultrabiomicroscopy (UBM), we demonstrated that the performance of the ciliary muscle is diminished and accompanied by rigidity of the lens. Both lens thickness and trabecular-ciliary process distance (TCPD) were the parameters that showed major alterations with the loss of accommodation in patients of different ages. The results indicated that the differences between these parameters in farsightedness and nearsightedness in the different groups of patients were positively correlated

La resistencia bacteriana y sus mecanismos de dispersión

Fil: ORMAN, BETINA. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina.La utilización masiva de antibióticos en el medio hospitalario y en la comunidad da lugar a la selección de bacterias multirresistentes, o sea que una cepa bacteriana porta la resistencia a más de un antibiótico. Este fenómeno muestra la importancia del estudio de la diseminación de la resistencia por la aparición de cepas cada vez más resistentes

Autoantibodies against cerebral muscarinic cholinoceptors in Sjögren syndrome: Functional and pathological implications

Previous studies have demonstrated that antibodies against muscarinic acetylcholine receptors (mAChRs) from exocrine glands, correlates with Sjögren syndrome (SS) in the majority of patients. The aim of the present investigation was to establish if serum IgG antibodies present in SS interacts with cerebral mAChRs. Results show that anti-cerebral IgG are present in the sera of 40% SS patients studied. Autoantibodies were able to interact with mAChRs of cerebral frontal cortex membranes inhibiting the [(3)H]QNB binding to its specific receptor. Moreover, tested by ELISA and dot blot they recognized the synthetic peptides corresponding to the second extracellular loop of human M(1) and M(3) mAChR. In addition, the corresponding affinity-purified anti-M(1) and anti-M(3) peptide IgGs displayed an agonistic activity, stimulating phosphoinositide hydrolysis. The results support the notion that serum IgG autoantibodies in SS patients target cerebral mAChRs may have some role in the pathogenesis of higher cognitive dysfunction present in SS patients.Fil: Reina, Silvia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Catolica de Las Misiones; ArgentinaFil: Sterin Borda, Leonor. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Signaling pathways leading to prostaglandin E2 production by rat cerebral frontal cortex

In this paper, we have determined the effect of both muscarinic acetylcholine receptor (mAChR) and exogenous prostaglandin E(2) (PGE(2)) on PGE(2) production and cyclooxygenases (COX) mRNA gene expression on rat cerebral frontal cortex. Carbachol and PGE(2) increase endogenous PGE(2) production and the COX-1 mRNA levels by activation of PLA(2)s. The COX-1 and COX-2 activity participated in the production of PGE(2) triggered by exogenous PGE(2). While in carbachol-PGE(2) only COX-1 activity is affected. The specific inhibition of PGE(2) receptor was able to impair the increase of endogenous PGE(2) production triggered by both carbachol and exogenous PGE(2). These results suggest that carbachol-activation mAChR increased PGE(2) production that in turn interacting with its own receptor triggers an additional production of PGE(2). Both mechanisms appear to occur by using PLA(2) signaling system. This data should be able to contribute to understand the involvement of PGE(2) in normal brain function and its participation in neuroinflammatory processes.Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Reina, Silvia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Sterin Borda, Leonor Josefina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Borda, Enri Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentin

Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp

The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp.Fil: Sterin Borda, L.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: de Couto Pita, A.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin