Jeremías Gastón GallettiNational Scientific and Technical Research Council | conicet · IMEX Instituto de Medicina Experimental
Jeremías Gastón Galletti
MD PhD
About
48
Publications
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Introduction
I am an ophthalmologist and a clinician-scientist at the Institute of Experimental Medicine in Buenos Aires. My research is focused on the neuroimmunological aspects of ocular diseases, and we are currently investigating the mechanisms that drive corneal nerve damage in dry eye and other ocular surface disorders.
Additional affiliations
July 2004 - May 2012
August 2004 - present
June 2007 - December 2012
Publications
Publications (48)
Dry eye is an allegedly autoimmune disorder for which the initiating mechanisms and the targeted antigens in the ocular surface are not known, yet there is extensive evidence that a localized Th1/Th17 effector T cell response is responsible for its pathogenesis. In this work, we explore the reconciling hypothesis that desiccating stress, which is u...
Dry eye disease (DED) is a highly prevalent ocular surface disorder with neuroimmune pathophysiology. Tear hyperosmolarity (THO), a frequent finding in affected patients, is considered a key element in DED pathogenesis, yet existing animal models are based on subjecting the ocular surface to the more complex desiccating stress ‐decreased tear produ...
As the cornea is densely innervated, its nerves are integral not only to its structure but also to its pathophysiology. Corneal integrity depends on a protective tear film that is maintained by corneal sensation and the reflex arcs that control tearing and blinking. Furthermore, corneal nerves promote epithelial growth and local immunoregulation. T...
Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-med...
Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degenerati...
Dry eye disease (DED) is characterized by a dysfunctional tear film in which the corneal epithelium and its abundant nerves are affected by ocular desiccation and inflammation. Although adaptive immunity and specifically CD4 ⁺ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage rema...
Purpose
The purpose of this study was to investigate the effect of sodium hyaluronate (SH) on benzalkonium chloride (BAK)-induced toxicity in the ocular surface epithelium and corneal nerves.
Methods
Ocular surface epithelial cells from Balb/c mice were cultured with 0.1% to 0.4% SH and 0.001% to 0.01% BAK and their metabolic activity, viability,...
Background
To evaluate the prevalence of dry eye disease (DED) and its associated risk factors in a sample of the Argentine population.
Methods
A prospective cross-sectional population-based study was conducted in Argentina during April 2022 through an anonymous electronic survey that included participants aged 12 years old or older. The prevalenc...
Purpose:
CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice.
Methods:
Four-week female CD25KO mice...
Dry eye disease (DED) is characterized by a dysfunctional tear film in which the cornea epithelium and its abundant nerves are affected by ocular desiccation and inflammation. Although adaptive immunity and specifically CD4 ⁺ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage remai...
Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this inflammatory response by secreting Interleukin 1 bet...
Background: Corneal nerve damage causes the most clinically significant symptoms in dry eye disease (DED) yet its pathophysiology remains poorly understood. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal...
Purpose:
Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.
Methods:
Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulat...
Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6 J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6 J mice of different ages, we an...
Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-med...
Purpose: To evaluate the protective effect of different concentrations of sodium hyaluronate (SH) on the Benzalkonium chloride (BAK)-induced toxicity using an in vitro model.
Methods: The NAV14 cell line (SV40-immortalized murine conjunctival epithelium) was used. Cell monolayers were exposed to different combinations of BAK (0.001%; 0.005%; 0.01%)...
In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elev...
Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more select...
Neutrophils play major roles against bacteria and fungi infections not only due to their microbicide properties but also because they release mediators like Interleukin-1 beta (IL-1β) that contribute to orchestrate the inflammatory response. This cytokine is a leaderless protein synthesized in the cytoplasm as a precursor (pro-IL-1β) that is proteo...
Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57B...
The ocular surface is the part of the visual system directly exposed to the environment, and it comprises the cornea, the first refractive tissue layer, and its surrounding structures. The ocular surface has evolved to keep the cornea smooth and wet, a prerequisite for proper sight, and also protected. To this aim, the ocular surface is a bona fide...
Since the last century, advances in healthcare, housing, and education have led to an increase in life expectancy. Longevity is accompanied by a higher prevalence of age-related diseases, such as cancer, autoimmunity, diabetes, and infection, and part of this increase in disease incidence relates to the significant changes that aging brings about i...
Fever is a hallmark of infections and inflammatory diseases, represented by an increase of 1–4°C in core body temperature. Fever-range hyperthermia (FRH) has been shown to increase neutrophil recruitment to local sites of infection. Here, we evaluated the impact of a short period (1 h) of FRH (STFRH) on pro-inflammatory and bactericidal human neutr...
Objective: Data on treatment outcome for rheg-matogenous retinal detachment (RRD) in Latin American countries is scarce, thus we set out to determine anatomical outcome of surgery and its associated factors in two Argentine clinics. Methods: Retrospective review of patients presenting with primary RRD from 2012 to 2016 at two eye clinics in Buenos...
Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of t...
Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapid...
The ocular surface is constantly exposed to environmental irritants, allergens and pathogens, against which it can mount a prompt immune response to preserve its integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal immune system must also discriminate between harmless and potentially dangerous antigens, a seemingly complic...
Dry eye is a highly prevalent immune disorder characterized by a dysfunctional tear film and a Th1/Th17 T cell response at the ocular surface. The specificity of these pathogenic effector T cells remains to be determined, but auto-reactivity is considered likely. However, we have previously shown that ocular mucosal tolerance to an exogenous antige...
Purpose. To thoroughly analyze corneal deformation responses curves obtained by Ocular Response Analyzer (ORA) testing in order to improve subclinical keratoconus detection. Methods. Observational case series of 87 control and 73 subclinical keratoconus eyes. Examination included corneal topography, tomography, and biomechanical testing with ORA. F...
To evaluate intereye corneal asymmetry in Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) indices as a diagnostic method between normal patients and patients with keratoconus.
A retrospective, observational case series of 177 healthy, 44 indeterminate, and 121 patients with keratoconus classified by Pentacam ectasia detection indices, randomiz...
Purpose:
To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis.
Methods:
Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunizat...
Abstract Chronic lymphocytic leukemia (CLL) is the main cause of autoimmune hemolytic anemia (AHA). However, the cellular basis underlying this strong association remains unclear. We previously demonstrated that leukemic B cells from CLL patients recognize the erythrocyte protein Band 3, a prevalent autoantigen in AHA. Here we show that the major b...
Abstract
Purpose: To assess the state of conjunctival tolerance in a murine model of evaporative dry eye and to evaluate the effect of topical nuclear factor kappa B (NFkB) modulation on disease progression.
Methods: A previously reported murine model of evaporative dry eye (Niederkorn JY et al. J Immunol. 2006 Apr 1;176(7):3950-7) was used with 8...
To evaluate Pentacam ectasia detection indices in topographically-normal patients and in subclinical keratoconus cases.
Prospective, observational case series.
Setting: institutional; Patients: group 1 comprised one eye from 189 patients with unremarkable topography and groups 2 and 3 included the better and worse eyes, respectively, of 55 keratoco...
To evaluate inter-device agreement between Placido topography (iTrace; Tracey Technologies, Houston, TX) and Scheimpflug tomography (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany) for measuring corneal power and cylinder and axis of astigmatism.
Observational case series of 54 eyes from 54 subjects with no ocular disease. Main outcome measure...
To evaluate corneal biomechanical properties in non-keratoconic myopic eyes and to identify descriptors for improving the specificity of the Ocular Response Analyzer (ORA) (Reichert Ophthalmic Instruments, Depew, NY) testing for subclinical keratoconus detection.
Observational case series of 52 non-keratoconic non-myopic eyes and 97 non-keratoconic...
Purpose: To report anterior segment optical coherence tomography (AS-OCT) findings in corneas of keratoconus patients treated with riboflavin-ultraviolet-A-light-induced crosslinking (CXL).
Methods: Prospective, non-randomized, single-center clinical study that included 9 CXL-treated keratoconus eyes followed with corneal topography, specular micr...
The impact of topical eye drops with benzalkonium chloride (BAK) as a preservative could involve more than the reported toxic effects on the ocular surface epithelium and ultimately affect the immune balance of the conjunctiva. We found that BAK not only impairs tolerance induction in a murine model, but leads to mild systemic immunization. Contras...
To compare corneal hysteresis (CH) and corneal resistance factor (CRF) between normal eyes and eyes with keratoconus correcting for the effect of central corneal thickness (CCT) and to estimate keratoconus detection sensitivity and specificity of these parameters.
Observational case series of 102 normal eyes (control group) and 77 eyes with keratoc...
T cells from patients with chronic lymphocytic leukemia may play an important role in contributing to the onset, sustenance, and exacerbation of the disease by providing survival and proliferative signals to the leukemic clone within lymph nodes and bone marrow.
By performing chemotaxis assays towards CXCL12, CCL21 and CCL19, we sought to evaluate...
Resumen
objetIvo: Comunicar la presentación conjunta de síndrome de Saethre-Chotzen y queratocono en dos pacientes relacionados.
casos clínIcos: Dos hermanos con síndrome de Saethre-Chotzen y patrón ectásico corneal compatible con queratocono seguidos
durante años en nuestra División Oftalmología.
conclusIones: Si bien la asociación entre ambas pat...
The mechanisms underlying the frequent association between chronic lymphocytic leukemia (CLL) and autoimmune hemolytic anemia are currently unclear. The erythrocyte protein band 3 (B3) is one of the most frequently targeted Ags in autoimmune hemolytic anemia. In this study, we show that CLL cells specifically recognize B3 through a still unidentifi...
The mechanisms underlying the frequent association between chronic lymphocytic leukemia (CLL) and autoimmune hemolytic anemia (AHA) remain ill-defined. In AHA autoantibodies are mostly directed to the erythrocyte proteins band 3 (B3), Rh complex or glycophorins. We explored the possibility that CLL cells could initiate the autoimmune response by pr...
Resumen La leucemia linfática crónica (LLC) se asocia frecuentemente con anemia hemolítica autoinmune (AHA), pero los mecanismos responsables no se han dilucidado todavía. En la AHA los autoanticuerpos están dirigidos mayormente contra las proteínas del eritrocito banda 3 (B3), complejo Rh o glicoforinas. Nosotros investigamos la posibilidad de que...
Questions
Questions (4)
Which percentage of labeled T cells should I find in the peripheral lymph nodes after adoptive transfer of say 5-10 million labeled T cells? Is there a difference in efficiency between the intraperitoneal and intravenous routes? I find intraperitoneal injections to be very reproducible and reliable, whereas tail-vein injections can be quite variable from mouse to mouse. We just transferred 35 million CFSE-labeled CD3+ cells by intraperitoneal injection to 12 mice and we observed between 0.4-0.7% labeled cells in the popliteal and cervical lymph nodes 48 h later. I was expecting to find about 10 times that number...
I´m performing DTH assays in mice. I usually immunize with 100 ug OVA in complete Freund´s adjuvant (1:1 mixture) by a subcutaneous injection, wait for two weeks and then inject 100 ug heat-aggregated OVA in 50 ul in one of the footpads. I also inject the same volume of PBS in the other footpad to control for the unspecific swelling response. There is commonly up to 0.1 mm swelling in the control footpad and at most 0.3 mm swelling in the antigen-loaded footpad. I was hoping to obtain more swelling or at least more reproducible reactions so I don´t have to work with many mice per treatment group. Has anyone tried using 10- to 100-fold higher doses of antigen for the DTH reaction?
I'm evaluating the capacity of some epithelial cell supernatants to induce dendritic cell maturation. I take murine bone-marrow-derived dendritic cells on day 6 (DCs) and culture them for 48 h in the presence of culture medium alone (immature DCs), 1 ug/ml LPS (mature DCs) and my supernatants at 25% concentration. I observe a comparable increase in MHC II and CD86 expression in all treatments but in immature DCs, as expected. I then take the DCs, wash them twice and culture them again at a 1:10 ratio with CFSE-labelled allogeneic T cells. I observe significant proliferation with SN-exposed DCs on day 3 (up to 4-5 rounds of proliferation) and not with LPS (only 2-3 round) at this timepoint. If I wait up to day 5, LPS DCs induce proliferation similar to that observed for the SNs on day 3, and at this point, the SN DC culture have considerable cell death. I cannot conclude from these experiments that SN DCs are more efficient at T cell stimulation, can I? Do you have any suggestions? What do you think is going on in my experimental setup?
I have grade V ovalbumin. I have tried to heat a 20 mg/ml solution at 60 C for 10 min and I ended up with coagulated protein, almost like cooked egg white. Does anyone know of a good protocol for a delayed-type hypersensitivity reaction?
